The year 2020 reflected the continued growth in new drug approvals by the US Food and Drug Administration (FDA) that has been seen over the past few years. As the FDA has implemented new programs to streamline its review and approval processes, a total of 47 novel drugs were approved between January 1 and December 1, 2020.¹ Of these, 17 new products had indications in oncology, hematology, or supportive care.¹

To view the FDA Approvals of Oncology Products Table of Contents, click here.

First-in-Class Drug Approvals

Two new drugs approved this year represented first-in-class products (Table 1). Blenrep (belantamab mafodotin-blmf) is a B-cell maturation antigen (BCMA)-directed antibody and microtubule inhibitor conjugate. Its 3 components are an afucosylated humanized immunoglobulin G1 (IgG1) monoclonal antibody covalently linked to a microtubule inhibitor (monomethyl auristatin F) via a protease-resistant maleimidocaproyl linker. The approval of Blenrep for the treatment of relapsed or refractory multiple myeloma in patients who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent makes it the first approved anti-BCMA therapy.

While multiple myeloma is a relatively uncommon cancer, approximately 32,270 diagnoses and 12,830 deaths had been expected in 2020.² “The approval of Blenrep is an important advancement for patients with relapsed or refractory multiple myeloma, as it brings a much-needed new treatment to patients who face limited options due to their progressing disease,” Paul Giusti, president and chief executive officer of the Multiple Myeloma Research Foundation, said in a GlaxoSmithKline press release.³

Retevmo (selpercatinib), a kinase inhibitor (KI) that targets both wild-type and multiple mutated ret proto-oncogene (RET) isoforms, works by blocking the primary driver of tumor growth in RET-positive metastatic non–small-cell lung cancer (NSCLC) and advanced thyroid cancers. Retevmo is indicated for adult patients with metastatic RET fusion–positive NSCLC, adults and children aged 12 or older with advanced or metastatic RET-mutant medullary thyroid cancer requiring systemic therapy, and adults and children aged 12 or older with advanced or metastatic RET fusion–positive thyroid cancer requiring systemic therapy and who are radioactive iodine–refractory.⁴

First Products Approved in Their Indications

Several novel drugs offered treatment options for patients with cancers that had been previously untreatable or had had few treatment options available (Table 2).⁵

Ayvakit (avapritinib) is the first KI approved for the treatment of gastrointestinal stromal tumor (GIST). GISTs are not common; the estimated annual number of diagnosed US cases ranges from 4000 to 6000.⁶ Approximately 10% of GISTs have the platelet-derived growth factor receptor α gene (PDGFRA) sequence variation.⁷ Ayvakit was approved for patients with unresectable or metastatic GIST with PDGFRA exon 18 sequence variations, including PDGFRA D842V variations.

“[GISTs] harboring a PDGFRA exon 18 mutation do not respond to standard therapies for GIST,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in an FDA news release.⁸ “However, [the approval of Ayvakit] provides patients with the first drug specifically approved for GIST harboring this mutation,” he added.

Qinlock (ripretinib) was the first FDA-approved fourth-line treatment for advanced GIST. Ripretinib is indicated for adult patients who have previously received 3 or more KIs, including imatinib.

“Despite the progress that has been made over the past 20 years in developing treatments for GIST, including … avapritinib earlier this year—some patients don’t respond to treatment and their tumors continue to progress,” said Dr Pazdur in an FDA news release.⁹ The approval of Qinlock “provides a new treatment option for patients who have exhausted all FDA-approved therapies for GIST,” he continued.

Another new product that filled an unmet need was Tabrecta (capmatinib), which represented the first FDA approval of a drug specifically for NSCLC with specific sequence variations that lead to mesenchymal-epithelial transition (MET) exon 14 skipping. Capmatinib has a companion diagnostic, the FoundationOne CDx assay (F1CDx). The FDA approved this diagnostic test at the same time as Tabrecta; this next-generation sequencing is capable of detecting sequence variations that lead to MET exon 14 skipping.¹⁰

Pemazyre (pemigatinib) is the first FDA-approved drug to treat adults with locally advanced or metastatic, previously treated, advanced cholangiocarcinoma with tumors containing a fusion or other rearrangement of the fibroblast growth factor receptor 2 gene (FGFR2).¹¹

Cholangiocarcinoma is a rare cancer affecting the bile ducts. “These patients have no other good options following first line treatment with chemotherapy” Dr Pazdur said in an FDA press release.¹¹

Cerianna (fluoroestradiol F 18) is the first FDA-approved F 18 positron-emission tomography imaging agent specifically used for visual detection of estrogen receptor–positive lesions in persons with recurrent or metastatic breast cancer. Cerianna should be used in addition to tissue biopsy.¹²

The FDA approved Tazverik (tazemetostat) to treat adults and children aged 16 years or older with epithelioid sarcoma. Epithelioid sarcoma is a rare cancer, accounting for less than 1% of all soft-tissue carcinomas. Tazverik is the second targeted therapy for soft-tissue sarcoma and the first targeted therapy specifically for epithelioid sarcoma.¹³

New Uses for Already Approved Therapies

A continuing trend in 2020 has been the approval of new indications for existing drugs. In some cases, the expanded approvals granted to oncology products this year provided treatment options for diseases that had had no specific approved treatments available (Table 2).

Lynparza (olaparib) received expanded approval for adults with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed despite treatment with enzalutamide or abiraterone.¹⁴ Lynparza was also approved, in combination with bevacizumab, for first-line maintenance treatment of adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status (deleterious or suspected deleterious BRCA mutation and/or genomic instability.¹⁵

Rubraca (rucaparib) was granted accelerated expanded approval to treat patients with deleterious BRCA mutated (germline and/or somatic) mCRPC who have previously received androgen receptor–directed therapy and taxane-based chemotherapy.¹⁶

Pomalyst (pomalidomide) received accelerated approval for the expanded indication to include adults with AIDS-related Kaposi sarcoma following the failure of highly active antiretroviral therapy, as well as Kaposi sarcoma in adults who are HIV-negative.¹⁷

Retevmo (selpercatinib) was granted accelerated approval for 3 indications: (1) adults with metastatic RET fusion–positive NSCLC, (2) adults and children aged 12 years or older with advanced or metastatic RET-mutant medullary thyroid cancer requiring systemic therapy, and (3) adults and children aged 12 years or older with advanced or metastatic RET fusion–positive thyroid cancer requiring system therapy and who are radioactive iodine–refractory.¹⁸

Zejula (niraparib) received approval for maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to first-line platinum-based chemotherapy.¹⁹

Jelmyto (mitomycin) received FDA approval for treatment of adult patients with low-grade upper tract urothelial cancer.²⁰

Tecentriq (atezolizumab) was approved in combination with cobimetinib and vemurafenib for patients with BRAF V600 mutation–positive unresectable or metastatic melanoma.²¹

The FDA approved Inqovi, an oral combination of decitabine and cedazuridine, for adults with myelodysplastic syndrome (MDS) including those previously treated and untreated, de novo and secondary MDS with specific French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.²²

Phesgo, a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf for subcutaneous injection, was approved for the following indications: (1) in combination with chemotherapy as neoadjuvant treatment in persons with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (greater than 2 cm in diameter or node positive), (2) in combination with chemotherapy as adjuvant treatment of persons with HER2-positive early breast cancer at high risk of recurrence, and (3) use in combination with docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 treatment or chemotherapy.²³

Cyramza (ramucirumab) was approved in combination with erlotinib for first-line treatment of metastatic NSCLC with epidermal growth factor receptor gene (EGFR) exon 19 deletions or exon 21 sequence variations.²⁴

The FDA approved the combination use of Tecentriq (atezolizumab) and Avastin (bevacizumab) for patients with unresectable or metastatic hepatocellular carcinoma without any previous systemic therapy.²⁵

Braftovi (encorafenib) in combination with cetuximab was approved for the treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation.²⁶

Imfinzi (durvalumab) in combination with etoposide and either carboplatin or cisplatin was approved as first-line treatment for persons with extensive-stage small-cell lung cancer (ES-SCLC).²⁷

Nerlynx (neratinib) in combination with capecitabine received FDA approval for the treatment of adults with advanced or metastatic HER2-positive breast cancer who have received at least 2 previous anti-HER2–based regimens.²⁸

New Uses for Immunotherapies in Oncology

The year 2020 saw expanded indications for previously approved immunotherapies in oncology.

Opdivo (nivolumab) was granted additional approvals, in combination with Yervoy (ipilimumab), for patients with unresectable malignant pleural mesothelioma, patients with metastatic or recurrent NSCLC (including those expressing PD-L1) without EGFR or ALK tumor aberrations, and patients with hepatocellular carcinoma previously treated with sorafenib.

The FDA updated the indications for Keytruda (pembrolizumab), bringing the total number cancers approved to be treated with the drug to 15 this year. Among the indications added were first-line treatment of unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer and patients with bacillus Calmette-Guérin–unresponsive, high-risk, non-muscle–invasive bladder cancer with carcinoma in situ.

Pembrolizumab also received 2 new indications for Hodgkin lymphoma this year. The drug is now approved to treat patients with relapsed or refractory classical Hodgkin lymphoma (cHL) and to treat pediatric patients with refractory cHL or cHL that has relapsed with 2 other therapies.

Advances in Hematologic Malignancies

This year saw further development of approvals for specific types of leukemias and lymphomas for which the treatment landscape had not changed in decades. Mylotarg (gemtuzumab ozogamicin) was granted expanded approved for the treatment of newly diagnosed CD33-positive acute myeloid leukemia to include pediatric patients 1 month and older.²⁹ Imbruvica (ibrutinib) received an expanded indication, when combined with rituximab, for the initial treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.³⁰ Kyprolis (carfilzomib) and Darzalex (daratumumab) in combination with dexamethasone were approved for adult patients with relapsed or refractory multiple myeloma who have already received 1 to 3 lines of treatment.³¹

New Biosimilars for Oncology

The FDA approved 2 new biosimilars this year,³² one of which is used in patients with cancer. Nyvepria (pegfilgrastim-apgf) is a biosimilar to Neulasta (pegfilgrastim) to decrease the chance of infection as suggested by febrile neutropenia in patients with nonmyeloid cancer who are receiving myelosuppressive chemotherapy that has a clinically significant incidence of febrile neutropenia.³³

References

1. Novel drug approvals for 2020. Food and Drug Administration. Updated December 1, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2020

2. Key statistics about multiple myeloma. American Cancer Society. Updated January 8, 2020. Accessed December 3, 2020. https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html

3. FDA approves GSK’s Blenrep (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma. Press release. GlaxoSmithKline. August 6, 2020. Accessed December 3, 2020. https://www.gsk.com/en-gb/media/press-releases/fda-approves-gsk-s-blenrep-belantamab-mafodotin-blmf-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma

4. FDA approves first therapy for patients with lung and thyroid cancers with a certain genetic mutation or fusion. News release. Food and Drug Administration. May 8, 2020. Accessed December 3, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-patients-lung-and-thyroid-cancers-certain-genetic-mutation-or-fusion

5. Hematology/oncology (cancer) approvals & safety notifications. Food and Drug Administration. Updated December 1, 2020. Accessed December 3, 2020. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm

6. Key statistics for gastrointestinal stromal tumors. American Cancer Society. Accessed December 3, 2020. https://www.cancer.org/cancer/gastrointestinal-stromal-tumor/about/key-statistics.html.

7. Boonstra PA, Gietema JA, Suurmeijer AJH, et al. Tyrosine kinase inhibitor sensitive PDGFRA mutations in GIST: two cases and review of the literature. Oncotarget. 2017;8(65):109836-109847. Doi:10.18632/oncotarget.22663

8. FDA approves the first targeted therapy to treat rare mutation in patients with gastrointestinal stromal tumors. News release. Food and Drug Administration. January 9, 2020. Accessed December 3, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-rare-mutation-patients-gastrointestinal-stromal-tumors

9. FDA approves first drug for fourth-line treatment of advanced gastrointestinal stromal tumors. News release. Food and Drug Administration. May 15, 2020. Accessed December 3, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-fourth-line-treatment-advanced-gastrointestinal-stromal-tumors

10. FDA approves first targeted therapy to treat aggressive form of lung cancer. News Release. Food and Drug Administration. May 6, 2020. Accessed December 3, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer

11. FDA approves first targeted treatment for patients with cholangiocarcinoma, a cancer of bile ducts. Food and Drug Administration. News Release. April 17, 2020. Accessed December 3, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-treatment-patients-cholangiocarcinoma-cancer-bile-ducts

12. Drug trial snapshot: Cerianna. Food and Drug Administration. Revised June 3, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-cerianna

13. Simon S. FDA approves Tazverik (tazemetostat) for epithelioid sarcoma. American Cancer Society. January 24, 2020. Accessed December 3, 2020. https://www.cancer.org/latest-news/fda-approves-tazverik-tazemetostat-for-epithelioid-sarcoma.html

14. FDA approves olaparib for HRR gene-mutated metastatic castration-resistant prostate cancer. Food and Drug Administration. May 20, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-hrr-gene-mutated-metastatic-castration-resistant-prostate-cancer

15. FDA approves olaparib plus bevacizumab as maintenance treatment for ovarian, fallopian tube, or primary peritoneal cancers. Food and Drug Administration. May 11, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary

16. FDA grants accelerated approval to rucaparib for BRCA-mutated metastatic castration-resistant prostate cancer. Food and Drug Administration. May 15, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/fda-grants-accelerated-approval-rucaparib-brca-mutated-metastatic-castration-resistant-prostate

17. FDA grants accelerated approval to pomalidomide for Kaposi sarcoma. Food and Drug Administration. May 15, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pomalidomide-kaposi-sarcoma

18. FDA approves selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. Food and Drug Administration. May 11, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-selpercatinib-lung-and-thyroid-cancers-ret-gene-mutations-or-fusions

19. FDA approves niraparib for first-line maintenance of advanced ovarian cancer. Food and Drug Administration. April 29, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer

20. FDA approves mitomycin for low-grade upper tract urothelial cancer. Food and Drug Administration. April 15, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-low-grade-upper-tract-urothelial-cancer

21. FDA approves atezolizumab for BRAF V600 unresectable or metastatic melanoma. Food and Drug Administration. July 31, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-braf-v600-unresectable-or-metastatic-melanoma

22. FDA approves oral combination of decitabine and cedazuridine for myelodysplastic syndromes. Food and Drug Administration. July 7, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-oral-combination-decitabine-and-cedazuridine-myelodysplastic-syndromes

23. FDA approves combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf for HER2-positive breast cancer. Food and Drug Administration. June 29, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-combination-pertuzumab-trastuzumab-and-hyaluronidase-zzxf-her2-positive-breast-cancer

24. FDA approves ramucirumab plus erlotinib for first-line metastatic NSCLC. Food and Drug Administration. June 1, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-ramucirumab-plus-erlotinib-first-line-metastatic-nsclc

25. FDA approves atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. Food and Drug Administration. June 1, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-atezolizumab-plus-bevacizumab-unresectable-hepatocellular-carcinoma

26. FDA approves encorafenib in combination with cetuximab for metastatic colorectal cancer with a BRAF V600E mutation. Food and Drug Administration. April 9, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-encorafenib-combination-cetuximab-metastatic-colorectal-cancer-braf-v600e-mutation

27. FDA approves durvalumab for extensive-stage small cell lung cancer. Food and Drug Administration. March 20, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer

28. FDA approves neratinib for metastatic HER2-positive breast cancer. Food and Drug Administration. February 26, 2020. Accessed December 3, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neratinib-metastatic-her2-positive-breast-cancer

Table of Contents

Index: 2020 FDA Approvals of Oncology Products by Indication

Solid Cancers

Breast Cancer

Skin Cancer

Sarcoma

Neurofibromatosis

Non–Small-Cell Lung Cancer

Small-Cell Lung Cancer

Thyroid Cancer

Liver Cancer

Bile Duct Cancer

Gastrointestinal Stromal Tumors

Esophageal Cancer

Colorectal Cancer

Prostate Cancer

Ovarian, Fallopian Tube, or Peritoneal Cancer

Mesothelioma

Bladder Cancer

Hematologic Malignancies

Diffuse Large B-Cell Lymphoma

Follicular Lymphoma

Multiple Myeloma

Leukemia

Lymphoma

Diagnostic Tests/Imaging

Supportive Treatment

Index: 2020 FDA Approvals of Oncology Products by Indication

Solid Tumors

BREAST CANCER

KEYTRUDA (pembrolizumab)

Manufacturer: Merck

Approval Date: November 13, 2020

Keytruda was granted accelerated approval, in combination with chemotherapy, for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) with tumors that express PD-L1 as determined by an FDA-approved test.

The FDA approved the PD-L1 IHC 22C3 pharmDx companion diagnostic, manufactured by Dako North America, for selecting patients with TNBC for pembrolizumab.

Approval of Keytruda for TNBC was based on results of KEYNOTE-355, a multicenter, double-blind, randomized, placebo-controlled trial. Patients in the study had locally recurrent unresectable or metastatic TNBC and had not previously been treated with chemotherapy. The main efficacy outcome was progression-free survival (PFS). The study demonstrated a median PFS (mPFS) of 9.7 months (95% CI, 7.6-11.3) in patients who received pembrolizumab and chemotherapy compared with a mPFS of 5.6 months (95% CI, 5.3-7.5) in the placebo arm (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86, 1-sided P = .0012).

The most common adverse effects were fatigue, nausea, diarrhea, constipation, vomiting, alopecia, rash, cough, decreased appetite, and headache. Common laboratory abnormalities were anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia, elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hyperglycemia, hypoalbuminemia, elevated alkaline phosphatase (ALP), hypocalcemia, hyponatremia, hypophosphatemia, and hypokalemia.

The recommended dose of pembrolizumab for TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks, administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.

TRODELVY (sacituzumab govitecan-hziy)

Manufacturer: Immunomedics

Approval Date: April 22, 2020

Trodelvy, indicated for the treatment of adults with metastatic TNBC who have received at least 2 prior therapies, was granted FDA approval under the accelerated approval program.

FDA approval was granted based on results of the IMMU-132-01 trial, a multicenter, single-arm trial of 108 patients. The primary efficacy outcomes were overall response rate (ORR) and duration of response (DOR). The ORR was 33.3% (95% CI, 24.6-43.1), and the median DOR was 7.7 months (95% CI, 4.9-10.8).

The most common adverse effects of Trodelvy were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, hair loss, constipation, rash, decreased appetite, and abdominal pain.

Trodelvy is administered via intravenous (IV) infusion by a health care provider once weekly on days 1 and 8 of 21-day treatment cycles.

TUKYSA (tucatinib)

Manufacturer: Seattle Genetics

Approval Date: April 17, 2020

FDA approval of Tukysa was granted based on data from HER2CLIMB, a trial of 601 patients who had human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and had previously received treatment. Patients received tucatinib or placebo twice daily, in combination with trastuzumab and capecitabine. Treatment continued until the disease progressed or adverse effects were too toxic. The trial measured PFS.

PFS in patients taking Tukysa was 7.8 months (95% CI, 7.5-9.6) compared with 5.6 months (95% CI, 4.2-7.1) in patients receiving placebo (HR, 0.54; 95% CI, 0.42-0.71; P < .00001).

Tukysa may cause serious adverse effects, including severe diarrhea, liver damage, and fetal harm. The most common adverse effects were diarrhea, palmar-plantar erythrodysesthesia, nausea, tiredness, liver toxicity, vomiting, and mouth sores.

Tukysa is administered orally twice daily in combination with trastuzumab and capecitabine.

PHESGO (pertuzumab, trastuzumab, and
hyaluronidase-zzxf)

Manufacturer: Genentech

Approval Date: June 29, 2020

Phesgo, a fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf administered via subcutaneous infusion, was approved by the FDA for the following indications: use in combination chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer; use in combination chemotherapy as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence; and use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Approval was granted from results of FeDeriCa, an open-label, multicenter, randomized trial with 500 patients who had operable or locally advanced HER2-positive breast cancer. Patients received neoadjuvant chemotherapy with concurrent administration of either Phesgo or IV pertuzumab and IV trastuzumab.

The primary end point was noninferiority of cycle 7 pertuzumab serum trough concentration comparing Phesgo with IV pertuzumab. The secondary end points were cycle 7 trastuzumab serum trough concentration, pathological complete response, and safety.

Phesgo demonstrated noninferior pertuzumab and trastuzumab serum trough concentrations. The pathological complete response rate was 59.7% (95% CI, 53.3-65.8) in patients who received Phesgo and 59.5% (95% CI, 53.2-65.6) in patients who received IV pertuzumab and trastuzumab.

The most common adverse effects were alopecia, nausea, diarrhea, anemia, and asthenia.

Phesgo is administered subcutaneously over approximately 8 minutes for the first dose. The initial dose is a fixed 1200 mg of pertuzumab, 600 mg of trastuzumab, and 30,000 units of hyaluronidase, which is followed every 3 weeks with a fixed-dose rate of 600 mg of pertuzumab, 600 mg of trastuzumab, and 20,000 units of hyaluronidase administered over approximately 5 minutes.

NERLYNX (neratinib)

Manufacturer: Puma Biotechnology

Approval Date: February 25, 2020

Nerlynx, in combination with capecitabine, is indicated for adult patients with advanced or metastatic HER2-positive breast cancer who have received at least 2 prior anti-HER2–based regimens. FDA approval was granted based on data gathered from NALA, a randomized, multicenter, open-label clinical trial in 621 patients with metastatic HER2-positive breast cancer. Patients received either oral neratinib 240 mg daily on days 1 to 21 in combination with capecitabine twice daily on days 1 to 14 or oral lapatinib 1250 mg once daily on days 1 to 21 with oral capecitabine twice daily on days 1 to 14. The primary outcome PFS and overall survival.

The mPFS for patients who received neratinib was 5.6 months (95% CI, 4.9-6.9) and 5.5 months (95% CI, 4.3-5.6) in patients who received lapatinib. The median overall survival was 21 months (95% CI, 17.7-23.8) in patients receiving neratinib and 18.7 months (95% CI, 15.5-21.2) in patients receiving lapatinib. The ORR was 32.8% (95% CI, 27.1-38.9) for patients receiving neratinib and 26.7% (95% CI, 21.5-32.4) in patients receiving lapatinib.

The most common adverse effects were diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, decreased weight, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distension, renal impairment, and muscle spasms.

Neratinib is dosed at 240 mg (6 tablets) given orally once daily with food, on days 1 to 21 of a 21-day cycle. Neratinib is given with capecitabine (750 mg/m²) given orally twice daily on days 1 to 14.

SKIN CANCER

TECENTRIQ (atezolizumab)

Manufacturer: Genentech

Approval Date: July 30, 2020

FDA approval was granted to Tecentriq, in combination with cobimetinib and vemurafenib, for patients
with BRAF V600 mutation–positive unresectable or metastatic melanoma.

Approval was granted based on results of IMspire150, a double-blind, randomized, placebo-controlled, multicenter trial in 514 patients. After 28 days of cobimetinib and vemurafenib, patients received either atezolizumab 840 mg IV infusions every 2 weeks in combination with cobimetinib 60 mg orally once daily and vemurafenib 720 mg orally twice daily, or placebo in combination with cobimetinib 60 mg orally once daily (21 days on, 7 days off) and vemurafenib 960 mg orally twice daily.

The primary outcome was PFS. The mPFS for patients receiving Tecentriq was 15.1 months (95% CI, 11.4-18.4) and 10.6 months (95% CI, 9.3-12.7) for patients receiving placebo.

The most common adverse effects were rash, musculoskeletal pain, nausea, fatigue, hepatotoxicity, pyrexia, pruritus, edema, stomatitis, hypothyroidism, and photosensitivity.

The recommended dose, following 28 days of cobimetinib and vemurafenib, is 840 mg IV every 2 weeks, in combination with cobimetinib 60 mg orally daily (21 days on, 7 days off) and vemurafenib 720 mg orally twice daily.

KEYTRUDA (pembrolizumab)

Manufacturer: Merck

Approval Date: June 24, 2020

Keytruda was granted FDA approval for patients with recurrent or metastatic cutaneous squamous cell carcinoma not curable by surgery or radiation, based on results of the KEYNOTE-629 trial. This multicenter, multi-cohort, nonrandomized, open-label trial administered pembrolizumab 200 mg IV every 3 weeks to patients until disease progression or unacceptable toxicity, or a maximum of
12 months. This study excluded patients who had previously received therapy with an anti–PD-1, anti–PD-L1, or anti–CTLA-4 antibody and patients with autoimmune disease or a medical condition that requires immunosuppression. The main efficacy outcome of the study was ORR and DOR.

The ORR was 34% (95% CI, 24-44) and the median DOR was not reached (range 2.7, 13.1+ months).

The most common adverse effects were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

Keytruda is associated with immune-mediated adverse effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.

The recommended dose of Keytruda is 200 mg IV every 3 weeks or 400 mg IV every 6 weeks.

SARCOMA

TAZVERIK (tazemetostat)

Manufacturer: Epizyme

Approval Date: January 23, 2020

Tazverik is indicated for patients aged 16 years or older with metastatic and unresectable advanced epithelioid sarcoma. Tazemetostat was granted FDA approval under the accelerated approval program based on a trial of 62 patients with advanced epithelial sarcoma. Patients received Tazverik twice daily until disease progression or unacceptable toxicity. The benefit was measured by the ORR of patients experiencing partial or complete tumor shrinkage and how long the shrinkage lasted.

Of the 62 patients who received tazemetostat, 15% (95% CI, 7%-26%) had partial or complete tumor shrinkage. In 67% of these patients who experienced tumor shrinkage, the shrinkage lasted for 6 months or longer.

Serious adverse effects of Tazverik are development of other cancers and fetal harm. Common adverse effects include pain, tiredness, nausea, decreased appetite, vomiting, and constipation.

Four tablets (800 mg) of tazemetostat are taken orally twice daily.

POMALYST (pomalidomide)

Manufacturer: Celgene

Approval Date: May 14, 2020.

The FDA expanded the approval of Pomalyst to include treating adults with AIDS-related Kaposi sarcoma after the failure of highly active antiretroviral therapy and Kaposi sarcoma in adults who are HIV-negative.

Results from Study 12-C-0047, an open-label, single-arm clinical trial, demonstrated efficacy to drive FDA approval. The study administered 5 mg of pomalidomide orally once daily on days 1 through 21 of a 28-day cycle until disease progression or unacceptable toxicity. In total, 28 patients participated in the study. The main outcome was ORR, which included complete response, clinical complete response, and partial response.

Of the 18 patients with HIV, 67% (95% CI, 41-87) had an ORR, and the median DOR was 12.5 months (95% CI, 6.5-24.9). The 10 patients who did not have HIV had an ORR of 80% (95% CI, 44-98), with a median DOR of 10.5 months (95% CI, 3.9-24.2).

The most common adverse effects (including laboratory abnormalities) were decreased absolute neutrophil count or white blood cells; elevated creatinine or glucose; rash; constipation; fatigue; decreased hemoglobin, platelets, phosphate, albumin, or calcium; increased ALT; nausea; and diarrhea.

Pomalidomide is administered orally, 5 mg once daily, without regard to food. It is administered on days 1 to 21 of each 28-day cycle until disease progression or unacceptable toxicity. Highly active antiretroviral therapy for HIV treatment should be continued during treatment with Pomalyst.

NEUROFIBROMATOSIS

KOSELUGO (selumetinib)

Manufacturer: AstraZeneca

Approval Date: April 10, 2020

FDA approval for selumetinib, indicated for pediatric patients aged 2 years and older with neurofibromatosis type 1 (NF1) with symptomatic, inoperable plexiform neurofibromas (PN) was granted based on results from the SPRINT trial. This trial, sponsored by the National Cancer Institute, was an open-label, multicenter, single-arm trial in pediatric patients with NF1 and a measurable target PN that could not be surgically removed. Patients in the efficacy population were required to have at least one significant morbidity related to the target PN. These included disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder or bowel dysfunction. The main outcome measure was ORR.

The ORR was 66% (95% CI, 51-79). All patients who received Koselugo had a partial response rate, 82% of whom had sustained responses of at least 12 months. An independent review of the ORR using the same criteria showed it to be 44% (95% CI, 30-59).

The most common adverse events were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain, fever, acne, stomatitis, headache, paronychia, and pruritus.

Selumetinib can cause serious cardiomyopathy, ocular toxicity, and increased creatinine phosphokinase. Based on the severity of these symptoms, Koselugo should be withheld, dose-adjusted, or permanently discontinued if these reactions occur.

Selumetinib is dosed orally, 25 mg/m² twice daily, given on an empty stomach.

NON–SMALL-CELL LUNG CANCER

RETEVMO (selpercatinib)

Manufacturer: Eli Lilly

Approval Date: May 8, 2020

The FDA granted approval of selpercatinib under the accelerated approval program based on evidence from a trial of 702 patients aged 15 to 92 years, with certain cancers caused by abnormal RET genes. This trial included patients with non–small-cell lung cancer (NSCLC), medullary thyroid cancer, and thyroid cancer. Some patients had received previous treatments while others were treatment naive. All patients received Retevmo orally twice daily until cancer progression or intolerable adverse effects. The benefit was measured by ORR (percent of patients with tumor shrinkage) and DOR.

Of the 105 patients with previously treated NSCLC, 64% experienced complete or partial tumor shrinkage (95% CI, 54%-73%), 81% of whom experienced this for a duration greater than 6 months. Of the 39 patients who were treatment naive, 85% (95% CI, 7%-94%) experienced tumor shrinkage, with 58% of those patients experiencing shrinkage that lasted greater than 6 months.

The most common adverse effects were changes in laboratory tests (increased liver enzymes, increased blood glucose, decreased white cell and platelet counts, decreased protein levels, decreased calcium, increased total cholesterol, increased creatinine, and decreased sodium), dry mouth, diarrhea, hypertension, fatigue, edema, rash, and constipation.

Retevmo is a capsule taken twice daily by mouth.

TECENTRIQ (atezolizumab)

Manufacturer: Genentech

Approval Date: May 18, 2020

Tecentriq was granted FDA approval for first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression or PD-L1 stained tumor-infiltrating immune cells covering 10% or more of the tumor area with no EGFR or ALK genomic tumor aberrations. The FDA also approved the Ventana PD-L1 Assay, manufactured by Ventana Medical Systems, as the companion diagnostic device for selecting patients for treatment with atezolizumab.

The IMpower110 trial, a multicenter, international, randomized, open-label trial in patients with stage IV NSCLC whose tumors express PD-L1 and who had not received prior chemotherapy, provided the evidence for FDA approval. Patients were randomly assigned to receive either atezolizumab 1200 mg every 3 weeks until disease progression or unacceptable toxicity, or platinum-based chemotherapy. The main efficacy outcome was overall survival.

The median overall survival in patients who received Tecentriq was 20.2 months (95% CI, 16.5-NE) compared with 13.1 months (95% CI, 7.4-16.5) in patients who received platinum-based chemotherapy. The mPFS was 8.1 months (95% CI, 6.8-11.0) in persons receiving atezolizumab and 5.0 months (95% CI, 4.2-5.7) in persons receiving platinum-based chemotherapy.

The most common adverse reaction was fatigue.

Tecentriq is administered IV over 60 minutes at a dose of 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.

TABRECTA (capmatinib)

Manufacturer: Novartis

Approval Date: May 6, 2020

FDA approval of Tabrecta under the accelerated approval program was based on the GEOMETRY clinical trial of 334 patients with metastatic NSCLC with MET mutation. Some patients had received previous treatment, and others were treatment naive. Patients received 400 mg of capmatinib twice daily until cancer progression or intolerable adverse effects. The benefit was measured by ORR through tumor shrinkage and by DOR.

Of the 28 patients who were treatment naive, 68% (95% CI, 48-84) experienced complete or partial tumor shrinkage with a treatment duration of 12.6 months (95% CI, 5.5-25.3). Of the 69 patients who had received previous treatment, the ORR was 41% (95% CI, 29-53) with a DOR of 9.7 months (95% CI, 5.5-13.0).

The most common adverse effects of Tabrecta are swelling of the hands and feet, nausea, tiredness, vomiting, dyspnea, and decreased appetite.

Capmatinib is an oral capsule, taken twice daily.

ALUNBRIG (brigatinib)

Manufacturer: ARIAD Pharmaceuticals

Approval Date: May 22, 2020

Alunbrig was granted FDA approval for the treatment of adults with anaplastic lymphoma kinase (ALK)-positive metastatic NSCLC as detected by an FDA-approved test. The FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular) as the companion diagnostic for brigatinib. Efficacy of Alunbrig was supported with data from the ALTA-1L trial, a randomized, open-label, multicenter trial in adult patients with advanced ALK-positive NSCLC who had not received previous ALK-targeted therapy. Patients in the trial were required to have an ALK rearrangement based on a local standard of care testing. The 275 patients were divided into 2 groups, one of which received brigatinib 180 mg orally once daily with a 7-day lead-in of 90 mg once daily, and the other of which received crizotinib 260 mg orally twice daily. The main efficacy outcome was PFS, with additional efficacy outcome measure of ORR.

The median PFS for patients who received Alunbrig was 24 months (95% CI,18.5-NE) compared with 11 months (95% CI, 9.2-12.9) in the crizotinib group. The ORR was 74% (95% CI, 66-81) for persons receiving brigatinib and 62% (95% CI, 53-70) in patients receiving crizotinib.

The main adverse effects were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, and dyspnea.

Alunbrig is administered at a dose of 90 mg orally once daily for the first week and 180 mg once daily thereafter. Alunbrig can be administered with or without food.

GAVRETO (pralsetinib)

Manufacturer: Blueprint Medicines

Approval Date: September 4, 2020

The FDA granted approval to pralsetinib for adult patients with metastatic NSCLC that is caused by abnormal RET genes.

Approval under the FDA’s accelerated approval program was based on evidence from a clinical trial composed of 220 patients aged 26 to 87 years who had NSCLC caused by abnormal RET genes. Some patients had previously been treated for metastatic NSCLC and others were treatment naive. All patients received Gavreto orally once daily until cancer progression or intolerable adverse effects. The benefits were measured by the ORR of patients achieving complete or partial tumor shrinkage and by DOR.

In patients with previously treated NSCLC, 57% (95% CI,46%-68%) of the 87 patients experienced complete or partial tumor shrinkage. For 80% of patients, shrinkage lasted greater than 6 months. In patients who had never received treatment (27 total), 70% (95% CI, 50%-86%) had completed or partial tumor shrinkage. For 58% of patients, shrinkage lasted greater than 6 months.

The most common adverse reactions reported for pralsetinib are tiredness, constipation, joint and muscle pain, and increased blood pressure. The most common laboratory abnormalities are increased liver enzymes, increased creatinine, and decreased blood cell counts.

The recommended dose of pralsetinib, an oral capsule, is 400 mg (4 capsules) taken once daily on an empty stomach.

CYRAMZA (ramucirumab)

Manufacturer: Eli Lilly

Approval Date: May 29, 2020

Cyramza was approved by the FDA, in combination with erlotinib, for first-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) sequence variations. Approval was granted based on efficacy from the RELAY trial. This multinational, randomized, double-blind, placebo-controlled, multicenter study of 449 patients comprised patients with previously untreated metastatic NSCLC with tumors that had EGFR exon 19 deletion or exon 21 substitutions. Patients received either ramucirumab 10 mg/kg or placebo via IV infusion every 2 weeks, in combination with erlotinib 150 mg orally daily, until disease progression or unacceptable toxicity. The main efficacy outcome was PFS and additional outcomes were overall survival, ORR, and DOR.

The median PFS was 19.4 months in patients receiving ramucirumab compared with 12.4 months in those who did not receive ramucirumab. The ORR was 76% in patients receiving ramucirumab and 75% in those who received placebo, with a median DOR of 18.0 months and 11.1 months, respectively.

The most common adverse events were infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. The most common laboratory abnormalities were increased ALT, increased AST, anemia, thrombocytopenia, neutropenia, increased ALP, and hypokalemia.

Ramucirumab is administered via IV infusion at a dose of 10 mg/kg every 2 weeks.

OPDIVO and YERVOY (nivolumab and
ipilimumab)

Manufacturer: Bristol Myers Squibb

Approval Dates: May 15, 2020, and May 26, 2020

The combination of Opdivo and Yervoy received FDA approval for first-line treatment of patients with metastatic NSCLC with tumors that express PD-L1, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. The FDA approved the PD-L1 28-8 pharmDx diagnostic test, manufactured by Agilent Technologies, as a companion diagnostic test.

Initial approval was granted based on results from the CheckMate-227 trial. This randomized, open-label, multipart trial included patients with metastatic or recurrent NSCLC and no prior anticancer therapy. Part 1a of the trial included 793 patients with PD-L1 tumor expression who were randomly assigned to nivolumab and ipilimumab or platinum-doublet chemotherapy.

There was a statistically significant improvement in overall survival; patients who received the combination of Opdivo and Yervoy had a median overall survival of 17.1 months (95% CI, 15.0-20.1) compared with 14.9 months (95% CI, 12.7-16.7) in patients who received platinum-doublet chemotherapy. The mPFS in patients who received nivolumab and ipilimumab was 5.1 months (95% CI, 4.1-6.3) compared with 5.6 months (95% CI, 4.6-5.8) in the platinum-doublet chemotherapy arm. Median DOR was 23.2 months in Opdivo and Yervoy patients and 6.2 months in chemotherapy patients.

This combination was also approved as first-line treatment for patients with metastatic or recurrent NSCLC with no EGFR or anaplastic ALK genomic tumor aberrations in combination with 2 cycles of platinum-doublet chemotherapy.

Approval was granted based on results of the CheckMate-9LA trial, a randomized open-label trial in patients with metastatic or recurrent NSCLC. The trial demonstrated a statistically significant benefit in overall survival in patients who received the combination therapy plus chemotherapy compared with patients receiving chemotherapy alone. The mPFS was 6.8 months (95% CI, 5.6-7.7) in patients who received Opdivo and Yervoy compared with 5 months (95% CI, 4.3-5.6) in the chemotherapy arm.

The most common adverse effects were fatigue, rash, decreased appetite, musculoskeletal pain, diarrhea/colitis, dyspnea, cough, pruritus, nausea, and hepatitis.

SMALL-CELL LUNG CANCER

ZEPZELCA (lurbinectedin)

Manufacturer: Pharma Mar

Approval Date: June 15, 2020

The FDA granted approval to lurbinectedin under the accelerated approval program based on evidence from the RECIST clinical trial consisting of 105 adults with metastatic small-cell lung cancer (SCLC). All patients had SCLC that had progressed on or after previous platinum-based therapy and received Zepzelca infusions once every 3 weeks until tumor progression or intolerable adverse effects. The benefit was measured in the ORR, percent of patients achieving complete or partial tumor shrinkage, and by measuring DOR.

Of the 105 patients with SCLC receiving lurbinectedin, 35% (95% CI, 26%-45%) experienced partial tumor shrinkage, with a median DOR of 5.3 months (95% CI, 4.1-6.4). The ORR was 30% (95% CI, 22%-40%) with a median DOR of 5.1 months (95% CI, 4.9-6.4).

The most common adverse effects are decreased blood cell counts; tiredness; increased creatinine, ALT, and blood glucose, and nausea.

Zepzelca is administered IV by a health care provider every 3 weeks over a 1-hour infusion period.

IMFINZI (durvalumab)

Manufacturer: AstraZeneca

Approval Date: March 30, 2020

FDA approval was granted to Imfinzi, in combination with etoposide and either carboplatin or cisplatin, as first-line treatment for patients with extensive-stage SCLC. Approval was granted based on results from CASPIAN, a randomized, multicenter, active-controlled, open-label trial. The study compared patients randomly assigned to receive durvalumab plus chemotherapy with patients receiving chemotherapy alone. The main efficacy outcome was overall survival; additional outcomes were PFS and ORR.

The median overall survival was 13.0 months (95% CI, 11.5-14.8) in patients who received durvalumab compared with 10.3 months (95% CI, 9.3-11.2) in patients receiving chemotherapy alone. The PFS in patients who received durvalumab was 5.1 months (95% CI, 4.7-6.2) compared with 5.4 months (95% CI, 4.8-6.2) in the chemotherapy alone group. The ORR was 68% (95% CI, 62%-73%) in persons who received Imfinzi and 58% (95% CI, 52%-63%) in patients who received chemotherapy.

The most common adverse effects were nausea, fatigue/asthenia, and alopecia.

Imfinzi should be administered prior to chemotherapy on the same day. The recommended dose is 1500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single agent.

THYROID CANCER

RETEVMO (selpercatinib)

Manufacturer: Eli Lilly

Approval Date: May 8, 2020

The FDA granted approval of selpercatinib under the accelerated approval program based on evidence from a trial of 702 patients, aged 15 to 92 years, with certain cancers caused by abnormal RET genes. This trial included patients with NSCLC, medullary thyroid cancer, and thyroid cancer. Some patients had received previous treatments while others were treatment naive. All patients received Retevmo orally twice daily until cancer progression or intolerable adverse effects. The benefit was measure by ORR (percent of patients with tumor shrinkage) and DOR.

Of the 105 patients with previously treated NSCLC, 64% experienced complete or partial tumor shrinkage (95% CI, 54%-73%), 81% of whom experienced this for a duration greater than 6 months. Of the 39 patients who were treatment naive, 85% (95% CI, 7%-94%) experienced tumor shrinkage, with 58% of those patients experiencing shrinkage that lasted greater than 6 months.

The most common adverse effects are changes in laboratory tests (increased liver enzymes, increased blood glucose, decreased white cell and platelet counts, decreased protein levels, decreased calcium, increased total cholesterol, increased creatinine, and decreased sodium), dry mouth, diarrhea, hypertension, fatigue, edema, rash, and constipation.

Retevmo is a capsule taken twice daily by mouth.

GAVRETO (pralsetinib)

Manufacturer: Blueprint Medicines

Approval Date: December 1, 2020

Gavreto received accelerated approval for adult and pediatric patients aged 12 years or older who have advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or who have RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine–refractory. The FDA also granted priority review, breakthrough therapy, and orphan drug designation to pralsetinib.

Approval was given from results of ARROW, an open-label, multicenter, multicohort clinical trial with patients who had tumors with RET alterations as identified by next-generation sequencing, fluorescence in situ hybridization, or other tests.

The main efficacy outcome was ORR and DOR. Efficacy was evaluated in patients (55 total) who had received prior treatment with cabozantinib or vandetanib, in patients (29 total) who had not received previous treatment with cabozantinib or vandetanib, and in patients (9 total) who were radioactive iodine–refractory.

Of the patients who had received previous treatment, the ORR was 60% (95% CI, 46%-73%). DOR lasted at least 6 months in 79% of these patients. Of the patients who had not received prior therapy, the overall response rate was 66% (95% CI, 46%-82%). The DOR was at least 6 months in 84% of these patients. The ORR was 89% (95% CI, 52%-100%) in patients who were radioactive iodine–refractory. All of the radioactive iodine–refractory patients experienced a DOR of at least 6 months.

The most common adverse effects were constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. The most common laboratory test abnormalities were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decrease calcium (corrected), decreased sodium, increased AST, increased ALT, decreased platelets, and increased ALP.

Gavreto is administered at a dose of 400 mg (four 100-mg capsules), given orally once daily on an empty stomach with no food intake at least 2 hours before and 1 hour after administration.

LIVER CANCER

OPDIVO and YERVOY (nivolumab and
ipilimumab)

Manufacturer: Bristol Myers Squibb

Approval Date: March 10, 2020

The FDA granted accelerated approval to the combination of Opdivo and Yervoy for patients with hepatocellular carcinoma who had previously received treatment with sorafenib. The approval was based on data from CheckMate-040, a multicenter, multiple cohort, open-label trial. In the trial, 49 patients received nivolumab 1 mg/kg with ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity. The main outcomes were ORR and DOR.

The ORR in patients receiving the combination therapy was 33% (95% CI, 20-48), with 4 patients achieving complete response and 12 achieving partial responses. The DOR ranged from 4.6 months to 30.5 months, with 31% of patients experiencing a response that lasted at least 2 years.

The most common adverse reactions were fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness.

The recommended dose of nivolumab is 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every day every 3 weeks for 4 doses, then nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks.

TECENTRIQ and AVASTIN (atezolizumab
and bevacizumab)

Manufacturer: Genentech

Approval Date: May 29, 2020

The FDA granted approval for the combination of Tecentriq and Avastin to treat patients with unresectable or metastatic hepatocellular carcinoma without prior systemic therapy. Efficacy was proven by the IMbrave150 trial, a multicenter, international, open-label, randomized trial. A total of 501 patients were randomly assigned to receive either IV atezolizumab and bevacizumab or sorafenib orally twice daily. The main outcome was overall survival and PFS.

The median overall survival was not reached in patients receiving atezolizumab and bevacizumab and was 13.2 months (95% CI, 10.4-NE) in patients who received sorafenib. The estimated mPFS was 6.8 months (95% CI, 5.8-8.3) in the combination therapy group compared with 4.3 months (95% CI, 4.0-5.6) in the sorafenib monotherapy group.

The most common adverse effects were hypertension, fatigue, and proteinuria.

Atezolizumab is dosed at 1200 mg, followed by 15 mg/kg bevacizumab on the same day every day for 3 weeks. If bevacizumab is discontinued, atezolizumab should be dosed at 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks.

BILE DUCT CANCER

PEMAZYRE (pemigatinib)

Manufacturer: Incyte

Approval Date: April 17, 2020

Pemazyre, approved under the FDA’s accelerated approval program, is indicated for the treatment of adults with cholangiocarcinoma with a specific abnormality in FGFR2, which is either metastatic or unresectable, and has previously been treated with chemotherapy.

The approval of pemigatinib is based on evidence from the FIGHT-202 clinical trial of 146 patients with locally advanced or metastatic bile duct cancer who had received previous treatment and had a specific abnormality in FGFR2. Patients received Pemazyre once daily for 14 days and then took 7 days off therapy. The 21-day cycle was repeated until disease progression or toxicity was too great. The trial measured the percentage of patients achieving partial or complete shrinkage of the cancer and the duration of shrinkage.

Of the 107 patients, 36% (95% CI, 27%-45%) achieved partial or complete tumor shrinkage. Cancer shrinkage lasted 6 months or longer in 63% of these patients and lasted 12 months or longer in 18% of the patients.

Serious adverse effects of Pemazyre include detachment of retina, increased phosphate levels in the blood, and fetal harm. The most common adverse effects are increased phosphate levels in the blood, hair loss, diarrhea, nail changes, fatigue, change of taste, and nausea.

Pemazyre is an oral tablet that is administered once daily for 14 days, followed by 7 days off therapy, for a total 21-day cycle.

GASTROINTESTINAL STROMAL TUMORS

QINLOCK (ripretinib)

Manufacturer: Deciphera Pharmaceuticals

Approval Date: May 15, 2020

Qinlock is approved for treatment of adult patients with gastrointestinal stromal tumor (GIST) whose disease cannot be surgically removed, has metastasized, or has been treated with at least 3 previous treatments. Qinlock was granted FDA approval based on the INVICTUS clinical trial of 129 patients with unresectable or metastatic GIST who had received at least 3 previous treatments.

One trial analyzed the benefits and adverse effects of ripretinib in patients. Patients received Qinlock or placebo once daily until disease progression or unacceptable adverse effects. The benefit was analyzed by PFS, comparing the length of time the tumors did not grow. The PFS for patients receiving ripretinib was 6.3 months (95% CI, 4.6-6.9), compared with a 1-month average (95% CI, 0.9-1.7) for patients receiving placebo.

The most common adverse effects are hair loss, tiredness, nausea, abdominal pain, constipation, muscle pain, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia, and vomiting.

Qinlock is an oral tablet dosed at 150 mg once daily with or without food.

AYVAKIT (avapritinib)

Manufacturer: Blueprint Medicines

Approval Date: January 9, 2020

Ayvakit was granted FDA approval for adult patients with GIST whose disease is caused by specific PDGFRA sequence variations and cannot be surgically removed or is metastatic. Approval was granted based upon the NAVIGATOR clinical trial analyzing 204 patients with GIST. Patients with unresectable or metastatic GIST and sequence variations on the PDGFRA exon 18 (including D842V) received avapritinib once daily until disease progression or unacceptable toxicity. The benefit of avapritinib was measured by the percentage of patients experiencing partial or complete shrinkage of the tumor, as well as duration of the shrinkage.

Of the patients, 84% (95% CI, 69%-93%) had complete or partial tumor shrinkage; complete response accounted for 7%, and partial response accounted for 77%. In 61% of these patients (22 persons), shrinkage lasted greater than 6 months.

Adverse effects of Ayvakit include swelling, nausea, tiredness, trouble thinking, vomiting, decreased appetite, diarrhea, hair color change, increase tear secretions, abdominal pain, constipation, rash, and dizziness.

Avapritinib is an oral tablet, taken once daily on an empty stomach.

ESOPHAGEAL CANCER

OPDIVO (nivolumab)

Manufacturer: Bristol Myers Squibb

Approval Date: June 10, 2020

Opdivo was granted FDA approval for treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

The ATTRACTION-3 trial, a multicenter, randomized, active-controlled, open-label trial of 419 patients with unresectable advanced, recurrent, or metastatic ESCC provided evidence for Opdivo approval. The major efficacy outcome was overall survival, with ORR, DOR, and PFS as additional outcome measures.

The median overall survival for patients who received nivolumab was 10.9 months compared with the 8.4-month overall survival who did not receive nivolumab. The overall survival benefit was observed regardless of tumor PD-L1 expression level. The ORR in patients who received nivolumab was 19.3% (95% CI, 13.7-26.0) and 21.5% (95% CI, 15.4-28.8) in those who did not receive nivolumab, with a median DOR of 6.9 months (95% CI, 5.4-11.1) and 3.9 months (95% CI, 2.8-4.2), respectively.

The main adverse effects were rash, decreased appetite, diarrhea, constipation, musculoskeletal pain, upper respiratory tract infection, cough, pyrexia, pneumonia, anemia, fatigue, pruritus, nausea, and hypothyroidism.

Opdivo is administered via IV infusion, at a dose of 240 mg ever 2 weeks or 480 mg every 4 weeks.

COLORECTAL CANCER

KEYTRUDA (pembrolizumab)

Manufacturer: Merck

Approval Date: June 29, 2020

Keytruda was granted FDA approval for first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. The approval was granted based on results of KEYNOTE-177, a multicenter, international, open-label, active-controlled, randomized trial of 307 patients with previously untreated unresectable or metastatic MSI-H or dMMR colorectal cancer. Patients received either pembrolizumab 200 mg IV every 3 weeks, or the investigator’s choice of mFOLFOX6 or FOLFIRI with or without bevacizumab or cetuximab IV every 2 weeks. The main efficacy outcomes were PFS and overall survival.

The median PFS in patients receiving Keytruda was 16.5 months (95% CI, 5.4-32.4), compared with 8.2 months (95% CI, 6.1, 10.2) in patients receiving chemotherapy. At the time of PFS analysis, overall survival data were not available.

The most common adverse reactions were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain.

Pembrolizumab is dosed at 200 mg via IV infusion every 3 weeks or 400 mg every 6 weeks.

BRAFTOVI (encorafenib)

Manufacturer: Array BioPharma

Approval Date: April 8, 2020

Braftovi was granted FDA approval with breakthrough therapy designation in combination with cetuximab for the treatment of patients with metastatic colorectal cancer with a BRAF V600E sequence variation. Approval was granted based on results of the BEACON trial, a randomized, active-controlled, open-label, multicenter trial. A total of 220 patients received 300 mg of encorafenib orally once daily in combination with cetuximab, and 221 patients received either irinotecan or FOLFIRI in combination with cetuximab. The main outcome was overall survival, and additional outcome measures were PFS, overall confirmed response, and DOR.

The median overall survival was 8.4 months (95% CI, 7.5-11.0) in patients who received encorafenib compared with 5.4 months (95% CI, 4.8-6.6) in the control arm. The mPFS was 4.2 months (95% CI, 3.7-5.4) in the encorafenib arm compared with 1.5 months (95% CI, 1.4-1.7) in the control arm. The overall response ratios were 20% (95% CI, 13%-29%) and 2% (95% CI, 0-7%) respectively. The DOR was 6.1 months (95% CI, 4.1-8.3) in persons receiving encorafenib and not yet reached (95% CI, 2.6-not reached) in the control arm.

The most common adverse effects were fatigue, nausea, diarrhea, dermatitis acneiform, abdominal pain, decreased appetite, arthralgia, and rash.

Braftovi is dosed at 300 mg orally once daily in combination with cetuximab.

PROSTATE CANCER

LYNPARZA (olaparib)

Manufacturer: AstraZeneca

Approval Date: May 19, 2020

Olaparib was granted priority review and breakthrough therapy designation when it was approved by the FDA. Olaparib is indicated for adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC), who have progressed following previous treatment with enzalutamide or abiraterone. Lynparza has been approved with its companion diagnostic test, FoundationOne Liquid CDx, to detect patients with mCRPC carrying germline BRCA1 or BRCA2 alterations.

Evidence for approval was supported by the PROfound trial, an open-label, multicenter trial in which 256 patients were randomly assigned to receive olaparib 300 mg twice daily and 131 patients were randomly assigned to receive either enzalutamide or abiraterone acetate. All study participants received a gonadotropin-releasing hormone analogue or had a previous bilateral orchiectomy. The patients were divided into 2 cohorts: Patients with mutations in BRCA1, BRCA2, or ATM were in cohort A, and patients with mutations among 12 other genes in the HRR pathway were in cohort B. The major efficacy outcome was radiologic PFS (rPFS) in cohort A, with the secondary endpoints being ORR in cohort A, rPFS in cohort A+B, and overall survival in cohort A.

Patients who received Lynparza had a median rPFS of 7.4 months compared with 3.6 months (HR, 0.34; 95% CI, 0.25-0.47; P < .0001) in persons who did not receive Lynparza. The overall survival was 19.1 months in patients who received Lynparza compared with 14.7 months (HR, 0.69; 95% CI, 0.5-0.97, P = .0175) in those who did not. The ORR was 33% in patients receiving Lynparza and 2% (P < .0001) in patients not receiving Lynparza. The rPFS in cohort A+B was a median of 5.8 months in patients who received Lynparza and 3.5 months (HR, 0.49; 95% CI, 0.38-0.63; P < .0001) in the patients who did not.

The most common adverse effects were anemia, nausea, fatigue, decreased appetite, diarrhea, vomiting, thrombocytopenia, cough, and dyspnea. Venous thromboembolic events occurred in 7% of patients receiving olaparib compared with 3.1% of those who did not receive olaparib.

Olaparib is dosed at 300 mg, taken orally twice daily with or without food.

RUBRACA (rucaparib)

Manufacturer: Clovis Oncology

Approval Date: May 15, 2020

The FDA granted approval to Rubraca for the treatment of patients with deleterious BRCA mutation–associated mCRPC based on the results of the TRITON2 trial. To receive Rubraca, patients must have previously been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The TRITON2 trial is an ongoing, multicenter, single-arm clinical trial of 115 patients with BRCA-mutated mCRPC who have previously been treated with androgen receptor–directed therapy and taxane-based therapy. Patients received Rubraca 600 mg orally twice daily as well as either a concomitant gonadotropin-releasing hormone analogue or a prior bilateral orchiectomy.  The ORR, assessed in 62 patients, was 44% (95% CI, 31-57). Fifteen of the 27 patients had a confirmed ORR and a DOR of 6 months or greater.

The common adverse effects were fatigue, nausea, anemia, increased ALT and AST, decreased appetite, rash, constipation, thrombocytopenia, vomiting, and diarrhea.

Rucaparib is administered orally, 600 mg twice daily, without regard to food. Patients receiving rucaparib for mCRPC also need to receive a gonadotropin-releasing hormone analogue or have had a bilateral orchiectomy.

OVARIAN, FALLOPIAN TUBE, OR PERITONEAL CANCER

ZEJULA (niraparib)

Manufacturer: GlaxoSmithKline

Approval Date: April 29, 2020

Zejula was granted FDA approval for maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy. Approval was based on data from PRIMA, a double-blind, placebo-controlled trial of 133 patients. The main efficacy outcome was PFS. The mPFS was first analyzed in a homologous recombination-deficient population, then in the overall population.

The mPFS in homologous recombination-deficient population was 21.9 months (95% CI, 19.3-NE) in patients who received Zejula compared with 10.4 months (95% CI, 8.1-21.1) in patients who received placebo. The mPFS in the overall population was 13.8 months (95% CI, 11.5-14.9) for patients who received niraparib compared with 8.2 months (95% CI, 7.3-8.5) for patients who received placebo.

The most common adverse effects were thrombocytopenia, anemia, nausea, fatigue, neutropenia, constipation, musculoskeletal pain, leukopenia, headache, insomnia, vomiting, dyspnea, decreased appetite, dizziness, cough, hypertension, AST and ALT elevation, and acute kidney injury.

Niraparib is administered orally, once daily. Dosing is weight-based: The recommended dose is 200 mg for patients weighing less than 77 kg or with a platelet count less than 150,000/µL, and 300 mg for patients weighing 77 kg or greater and with a platelet count of 150,000/µL or greater.

LYNPARZA (olaparib)

Manufacturer: AstraZeneca

Approval Date: May 8, 2020

The FDA expanded the indication of Lynparza to include its combination with bevacizumab for first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency–positive status, defined either by a deleterious or suspected deleterious BRCA mutation and/or genomic instability. The FDA approved Myriad myChoice CDx as a companion diagnostic for Lynparza.

Approval of the new indication was granted based on data from the PAOLA-1 trial, a randomized, double-blind, placebo-controlled, multicenter trial. The trial compared patients receiving olaparib plus bevacizumab versus placebo plus bevacizumab. The major efficacy outcome measure was PFS, with an additional outcome measure of overall survival.

The mPFS of patients with homologous recombination deficiency–positive tumors was 37.2 months in those who received olaparib and 17.7 months (HR, 0.33; 95% CI, 0.25-0.45) in those who did not. Overall survival data are not yet available.

The most common adverse effects are nausea, fatigue, anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache.

Olaparib is administered orally, 300 mg twice daily, taken without regard to food.

MESOTHELIOMA

OPDIVO and YERVOY (nivolumab and
ipilimumab)

Manufacturer: Bristol Myers Squibb

Approval Date: October 2, 2020

The combination of Opdivo and Yervoy was granted FDA approval for first-line treatment of adult patients with unresectable malignant pleural mesothelioma. Approval was granted based on results of CheckMate-743, a randomized, open-label trial. Patients received either nivolumab and ipilimumab for up to 2 years or 6 cycles of chemotherapy with cisplatin or carboplatin plus pemetrexed.

The trial showed a statistically significant improvement in overall survival for patients treated with Opdivo and Yervoy compared with chemotherapy. The median overall survival was 18.1 months (95% CI, 16.8-21.5) compared with 14.1 months (95% CI, 12.5-16.2), respectively. The mPFS was 6.8 months (95% CI, 5.6-7.4) in patients receiving nivolumab and ipilimumab and 7.2 months (95% CI, 6.9-8.1) in patients receiving chemotherapy. Patients receiving Opdivo and Yervoy had a median DOR of 11.0 months compared with 6.7 months in patients receiving chemotherapy.

The most common adverse effects were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus. Nivolumab was administered at a dose of 360 mg every 3 weeks, and ipilimumab was administered at a dose 1 mg/kg every 6 weeks until disease progression, unacceptable toxicity, or 2 years without disease progression.

BLADDER CANCER

BAVENCIO (avelumab)

Manufacturer: EMD Serono

Approval Date: June 30, 2020

FDA approval was granted to Bavencio, indicated for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. The approval was supported with evidence from the JAVELIN Bladder 100 trial, a randomized, multicenter, open-label trial of 700 patients with unresectable, locally advanced, or metastatic urothelial carcinoma that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy. Patients received either avelumab IV every 2 weeks plus best supportive care (BSC) or BSC alone.

Overall survival in patients with PD-L1–positive tumors was the main efficacy outcome. The mean overall survival in patients receiving avelumab was 21.4 months and 14.3 months (HR, 0.69; 95% CI, 0.56-0.86; P = .001) in BSC alone.

The most common adverse effects were fatigue, musculoskeletal pain, urinary tract infection, and rash.

Avelumab is administered via IV infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

JELMYTO (mitomycin)

Manufacturer: UroGen Pharma

Approval Date: April 15, 2020

FDA approval was granted to Jelmyto for adult patients with low-grade upper tract urothelial cancer. Approval was granted based on OLYMPUS, an ongoing, single-arm, multicenter trial of 71 patients. The patients were treatment-naive or had recurrent low-grade noninvasive upper tract urothelial cancer with at least 1 measurable papillary tumor located above the ureteropelvic junction. Patients received weekly Jelmyto 4 mg/mL via ureteral catheter or nephrostomy tube for 6 weeks. For patients with a complete response at 3 months, instillations were administered monthly for a maximum of 11 additional instillations. The major efficacy outcomes were complete response and complete response durability.

Of the patients receiving mitomycin, 58% achieved a complete response at 4 months and continued in follow-up. At least 29 of the patients received at least 1 dose of maintenance therapy. Durability of response was measured at 3, 6, 9, and 12 months. A total of 7 patients had documented recurrences, and 19 patients remained in complete remission at the 12-month mark.

The most common adverse effects were ureteric obstruction, flank pain, urinary tract infection, hematuria, renal dysfunction, fatigue, nausea, abdominal pain, dysuria, and vomiting. Ureteric obstruction occurred in 58% of the patients who received Jelmyto, and 88% of those patients required ureteral stent placement.

Mitomycin is administered at a dose of 4 mg/mL via ureteral catheter or nephrostomy tube with a total instillation volume not to exceed 15 mL.

KEYTRUDA (pembrolizumab)

Manufacturer: Merck

Approval Date: January 8, 2020

Keytruda was approved by the FDA for the treatment of patients with bacillus Calmette-Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Efficacy was established by the KEYNOTE-057 trial, a multicenter, single-arm trial with 148 patients with high-risk NMIBC, 96 of whom had BCG-unresponsive CIS with or without papillary tumors. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity, persistent or recurrent high-risk NMIBC; or progressive disease, or up to 24 months of therapy without disease progression. The major efficacy outcomes were complete response and DOR.

In the 96 patients who had high-risk BCG-unresponsive NMIBC with CIS, the complete response rate was 41% (95% CI, 31%-51%) with a median DOR of 16.2 months. Of the patients who responded to treatment, 46% experienced a complete response lasting at least 12 months.

The most common adverse effects were fatigue, diarrhea, rash, pruritus, musculoskeletal pain, hematuria, cough, arthralgia, nausea, constipation, urinary tract infection, peripheral edema, hypothyroidism, and nasopharyngitis.

Pembrolizumab is dosed at 200 mg every 3 weeks.

HEMATOLOGIC MALIGNANCIES

DIFFUSE LARGE B-CELL LYMPHOMA

MONJUVI (tafasitamab-cxix)

Manufacturer: MorphoSys

Approval Date: July 31, 2020

The FDA granted approval to Monjuvi under the accelerated approval program based on evidence from a clinical trial of 71 patients with diffuse large B-cell lymphoma (DLBCL). Monjuvi is to be used when patients cannot receive a stem-cell transplant. Monjuvi is a CD19-directed cytolytic antibody.

In the L-MIND trial, patients received tafasitamab-cxix (initially with lenalidomide, and then alone), and treatment continued until disease progression or unacceptable adverse effects. The benefit was best ORR, measuring how many patients had complete or partial tumor shrinkage. Of the patients, 55% (95% CI, 43%-67%) experienced complete or partial tumor shrinkage that lasted on average 21.7 months.

Common adverse effects of tafasitamab-cxix are low blood-cell count, fatigue, diarrhea, cough, fever, limb swelling, upper respiratory infection, and decreased appetite.

Monjuvi is administered by a health care professional via IV infusion. Monjuvi should be administered with lenalidomide 25 mg orally on days 1 to 21 of each 28-day cycle for a maximum of 12 cycles. Monjuvi should be continued as monotherapy until disease progression or unacceptable toxicity.

XPOVIO (selinexor)

Manufacturer: Karyopharm Therapeutics

Approval Date: June 22, 2020

FDA accelerated approval was based on the results of a multicenter, single-arm, open-label trial of patients with DLBCL. Xpovio is approved for adult patients with relapsed or refractory DLBCL after at least 2 lines of previous systemic therapy.

The study found that of the 134 patients, the ORR was 29% (95% CI, 22%-38%) with a complete response rate of 13%. Of the patients who achieved partial or complete response, 38% had response rates lasting at least 6 months, and 15% had response rates lasting at least 12 months.

The most common adverse effects were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Common laboratory abnormalities included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Nearly half of the study participants experienced serious adverse reactions, most of which were from infection.

Xpovio 60 mg is taken orally on days 1 and 3 of each week, given with antiemetic prophylaxis.

FOLLICULAR LYMPHOMA

TAZVERIK (tazemetostat)

Manufacturer: Epizyme

Approval Date: June 18, 2020

Accelerated FDA approval was granted to Tazverik, an enhancer of zeste homolog 2 (EZH2) inhibitor, for adult patients with relapsed or refractory follicular lymphoma with tumors positive for EZH2 sequence variation and who have received at least 2 prior systemic therapies or who have no other treatment options.

Approval was granted based on the 2 open-label, single-arm cohorts of patients who had previously received at least 2 prior systemic treatments with confirmed EZH2 variations. Efficacy was determined by ORR and DOR.

The response rate in the 42 patients with EZH2 variation was 69% (95% CI,53%-82%), 12% of whom had a complete response and 57% of whom had a partial response. The median DOR was 34% (95% CI, 22%-48%). In 53 patients with EZH2 wild-type mutation, the ORR was 34%, with 4% experiencing a complete response and 30% experiencing a partial response. The median DOR for this group was 13 months (95% CI, 5.6-NE).

The most common adverse effects were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and abdominal pain.

Tazverik is dosed at 800 mg and is taken orally twice daily with or without food.

MULTIPLE MYELOMA

BLENREP (belantamab mafodotin-blmf)

Manufacturer: GlaxoSmithKline

Approval Date: August 5, 2020

Approval of Blenrep under the FDA’s accelerated program was based on data from a trial of people with multiple myeloma (MM) whose disease came back after or did not respond to previous treatment. The benefit of belantamab mafodotin-blmf was measured by the ORR of patients who achieved improvement.

In the trial, 30 of the 97 patients (31%) (95% CI, 21%-43%) who received Blenrep had improvement in their disease. Of these patients, 73% experienced improvement that lasted at least 6 months.

Blenrep can cause serious changes to the cornea, leading to worsening vision or vision loss. Due to this adverse effect, Blenrep is available only through a Risk Evaluation and Mitigation Strategy (REMS) program. Other serious adverse effects include low platelet counts, infusion-related reactions, and fetal harm. Common adverse effects include corneal changes, decreased vision or blurred vision, nausea, low blood-cell counts, fever, infusion-related reactions, fatigue, and changes in kidney- or liver-function blood tests.

Blenrep is administered via IV infusion by a health care provider every 3 weeks, with the infusion taking approximately 30 minutes.

SARCLISA (isatuximab-irfc)

Manufacturer: Sanofi-Aventis

Approval Date: March 2, 2020

Sarclisa was approved based on one trial that evaluated the efficacy and adverse effects in persons who had previously treated MM. The trial was randomized and open-label, with patients receiving either isatuximab-irfc (combined with pomalidomide and low-dose dexamethasone) or the active comparator (pomalidomide and low-dose dexamethasone). The trial measured PFS.

Those receiving isatuximab had a longer PFS, with a median of 11.52 months (95% CI, 8.94-13.9) compared with patients who did not receive isatuximab, who had a median PFS of 6.47 months (95% CI, 4.47-8.28).

Serious adverse effects include infusion reactions, neutropenia, and possible development of new cancers. The most common adverse effects are low blood-cell counts, infusion reactions, pneumonia, upper respiratory infections, and diarrhea.

Sarclisa is administered by a health care provider via IV infusion every week for 4 weeks, then every 2 weeks thereafter. It is administered in combination with dexamethasone and pomalidomide.

KYPROLIS and DARZALEX (carfilzomib and
daratumumab)

Manufacturer: Onyx Pharmaceuticals (Kyprolis) and Janssen Biotech (Darzalex)

Approval Date: August 20, 2020

FDA approval was granted for the combination of carfilzomib, daratumumab, and dexamethasone for the treatment of patients with relapsed or refractory MM who have previously received 1 to 3 lines of therapy. Efficacy was determined based on the results of 2 trials, CANDOR and EQUULEUS.

CANDOR was a randomized, open-label, multicenter trial that evaluated carfilzomib in combination with IV daratumumab and dexamethasone (KdD) compared with carfilzomib and dexamethasone alone (Kd). A total of 466 patients participated in the study, with 321 receiving KdD and 154 receiving Kd. Efficacy was determined by the primary outcome, PFS. The mPFS was not reached in the KdD arm and was 15.8 months (95% CI, 12.1-NE) in the Kd arm (HR, 0.63; 95% CI, 0.46-0.85; 1-sided P = .0014).

EQUULEUS was an open-label, multicohort trial evaluated the KdD treatment regimen. Efficacy was determined by ORR. The ORR of the 85 patients in the study was 81% (95% CI, 71-89) with a DOR of 27.5 months.

The most common adverse effects were infusion-related reactions, anemia, diarrhea, fatigue, hypertension, pyrexia, respiratory tract infection, thrombocytopenia, neutropenia, lymphoma, cough, dyspnea, insomnia, headache, and back pain.

Carfilzomib and daratumumab are administered intravenously.

DARZALEX FASPRO (daratumumab and
hyaluronidase-fihj)

Manufacturer: Janssen Biotech

Approval Date: May 1, 2020

Darzalex Faspro was granted FDA approval for adult patients with newly diagnosed or relapsed/refractory MM. This new formulation allows for subcutaneous dosing of daratumumab. Daratumumab and hyaluronidase-fihj is approved for the following indications that IV daratumumab has previously been approved for:

In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem-cell transplant;

In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem-cell transplant and in patients with relapsed or refractory MM who have received at least 1 prior therapy;

In combination with bortezomib and dexamethasone in patients who have received at least 1 prior therapy; and

As monotherapy in patients who have received at least 3 prior lines of therapy including a proteasome inhibitor and immunomodulatory agent or who are double-refractory to a proteasome inhibitor and immunomodulatory agent.

Efficacy was evaluated in COLUMBA, an open-label noninferiority trial in which 263 patients to were randomly assigned to Darzalex Faspro and 259 to IV daratumumab. The trial had 2 primary end points: ORR and the maximum trough concentration on cycle 3, day 1 pre-dose.

Daratumumab hyaluronidase-fihj was noninferior to daratumumab IV for both primary end points. The ORR was 41.1% in patients who received Darzalex Faspro and 37.1% in patients who received IV daratumumab, with a risk ratio of 1.11 (95% CI, 0.89-1.37). The geometric mean ratio comparing Darzalex Faspro to IV daratumumab for maximum trough concentration was 108% (90% CI, 96-122).

Efficacy of daratumumab and hyaluronidase-fihj in combination with bortezomib, melphalan, and prednisone was evaluated in a single-arm cohort of PLEIADES, a multicohort, open-label trial. Patients had newly diagnosed MM and were ineligible for transplant. The main efficacy outcome measure was 88.1% (95% CI, 77.9-94.7).

Efficacy of Darzalex Faspro in combination with lenalidomide and dexamethasone was also evaluated in a single-arm cohort. Eligible patients had at least 1 prior line of therapy. The ORR was 90.8% (95% CI, 81.0-96.5).

The most common adverse effect with daratumumab and hyaluronidase-fihj monotherapy was upper respiratory tract infection. The main adverse effects of daratumumab and hyaluronidase-fihj in combination with bortezomib, melphalan, and prednisone are upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia vomiting, and back pain. The most common adverse reactions with daratumumab and hyaluronidase-fihj in combination with lenalidomide and dexamethasone are fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia, and dyspnea.

The most common hematologic laboratory abnormalities are decreased levels of leukocytes, lymphocytes, neutrophils, platelets, and hemoglobin.

Daratumumab and hyaluronidase-fihj is administered subcutaneously at a dose of 1800 mg of daratumumab and 30,000 units of hyaluronidase. The administration is given over 3 to 5 minutes.

LEUKEMIA

VENCLEXTA (venetoclax)

Manufacturers: AbbVie and Genentech

Approval Date: October 16, 2020

The FDA granted regular approval to Venclexta in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for newly diagnosed acute myeloid leukemia (AML) in adults aged 75 years or older or who have comorbidities precluding intensive induction chemotherapy. Venetoclax originally received accelerated approval for this indication in November 2018. Approval was based on confirmed efficacy from 2 randomized, double-blind, placebo-controlled trials.

In VIALE-A, persons received venetoclax plus azacitidine or placebo plus azacitidine. Efficacy was measured on improvement in overall survival. The median overall survival was 14.7 (95% CI, 11.9-18.7) months in persons treated with venetoclax plus azacitidine compared with 9.6 months (95% CI, 7.4-12.7) in persons treated with placebo. Additionally, patients receiving venetoclax had an improvement in completed remission; 37% (95% CI, 31%-43%) compared with 18% (12%-25%) for those receiving placebo.

In VIALE-C, persons received venetoclax plus LDAC or placebo plus LDAC. Efficacy was measured by complete remission rate and duration of complete remission. Patients receiving venetoclax plus LDAC had a complete remission rate of 27% (95% CI, 20%-35%) with a median duration of 11.1 months (95% CI, 6.1-not reached) compared with a 7.4% (95% CI, 2.4%-16%) complete remission rate with a median duration of 8.3 months (95% CI, 3.1-not reached) in the placebo group. Venetoclax plus LDAC did not significantly improve overall survival compared with placebo plus LDAC.

The most common adverse effects of venetoclax with azacitidine, decitabine, or LDAC were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, cough, oropharyngeal pain, and hypotension.

Venclexta is an oral tablet and is dose-dependent upon the chemotherapy regimen chosen.

ONUREG (azacitidine)

Manufacturer: Celgene

Approval Date: September 1, 2020

Onureg received priority review and orphan drug status by the FDA and is indicated for continued treatment of patients with AML who achieve first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy.

Approval was granted because of results from QUAZAR, a multicenter, randomized, double-blind, placebo-controlled trial. Following CR or CRi with intensive induction chemotherapy with or without receiving subsequent consolidation therapy, patients received either azacitidine 300 mg or placebo orally on days 1 to 14 of each 28-day cycle. The main efficacy outcome was overall survival. Median overall survival was 24.7 months (95% CI, 18.7-30.5) in persons receiving azacitidine and 14.8 months (95% CI, 11.7-17.6) in persons receiving placebo. There was consistent benefit in overall survival with azacitidine in CR and CRi patients alike.

Common adverse effects were nausea, vomiting, diarrhea, fatigue/asthenia, constipation, pneumonia, abdominal pain, arthralgia, decreased appetite, febrile neutropenia, dizziness, and pain in extremities.

Onureg is an oral tablet, dosed at 300 mg per day with or without food on days 1 to 14 of each 28-day cycle. Treatment with Onureg should continue until disease progression or unacceptable toxicity.

IMBRUVICA (ibrutinib)

Manufacturer: Pharmacyclics

Approval Date: April 21, 2020

The FDA expanded the indication of Imbruvica to include the initial treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in combination with rituximab. Approval was based on the E1912 trial, a 2:1 randomized, multicenter, open-label, actively controlled trial. Patients received either ibrutinib with rituximab or fludarabine, cyclophosphamide, and rituximab. The patients, 529 in total, were 70 years of age or younger with previously untreated CLL or SLL requiring systemic therapy. The main efficacy outcome was PFS.

The trial demonstrated a statistically significant improvement in PFS for patients who received ibrutinib and rituximab compared with fludarabine, cyclophosphamide, and rituximab (HR, 0.34; 95% CI, 0.22-0.5; P < .001). The median PFS was not reached after a median follow-up duration of 37 months.

The most common adverse effects were thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, and nausea.

Ibrutinib is administered orally, at a dose of 420 mg, taken once daily with water.

LYMPHOMA

KEYTRUDA (pembrolizumab)

Manufacturer: Merck

Approval Date: October 14, 2020

The approval of Keytruda was extended to treat adult patients with relapsed or refract classical Hodgkin lymphoma (cHL) and pediatric patients with refractory cHL or cHL that has relapsed following 2 or more lines of therapy.

Approval was granted based on the KEYNOTE-204 study. This phase III, randomized, open-label trial analyzed 304 adult patients with relapsed or refractory cHL who had already received at least 1 multiagent regimen. Patients received either pembrolizumab 200 mg every 3 weeks or brentuximab vedotin 1.8 mg/kg every 3 weeks, for up to 2 years.

Efficacy was based on PFS. The mPFS in persons receiving pembrolizumab was 13.2 months (95% CI, 10.9-19.4) and 8.3 months (95% CI, 5.7-8.8) in persons receiving brentuximab vedotin.

Serious adverse events occurred in 30% of patients receiving pembrolizumab. These included pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis.

Common adverse reactions were upper respiratory tract infection, musculoskeletal pain, diarrhea, cough, pyrexia, fatigue, and rash.

Pembrolizumab is recommended to be given as 200 mg every 3 weeks or 400 mg every 6 weeks IV in adults and 2 mg/kg every 3 weeks IV in pediatric patients, for up to 2 years.

TECARTUS (brexucabtagene autoleucel)

Manufacturer: Gilead

Approval Date: July 24, 2020

The FDA granted accelerated approval for Tecartus, indicated for treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). Tecartus was also granted orphan drug and breakthrough therapy designation.

Approval of the CD19-directed genetically modified autologous T-cell immunotherapy was based on results from ZUMA-2. The trial was an open-label, multicenter, single-arm trial of 74 patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine-kinase inhibitor. Patients received a single infusion of brexucabtagene autoleucel following completion of lymphodepleting chemotherapy. The primary efficacy outcome was ORR.

Of the 60 patients eligible for follow-up, 87% (95% CI, 75-94) experienced an ORR, 62% (95% CI, 48-74) of whom achieved complete remission. The overall DOR was 8.6 months and did not reach the estimated median DOR.

Serious adverse effects included anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection, pneumonia, hypocalcemia, and lymphopenia.

Tecartus has an associated REMS program due to the risk of cytokine release syndrome and neurologic toxicity.

Tecartus is administered as a single IV infusion of 2 × 10⁶ chimeric antigen receptor–positive viable T cells per kg body weight, preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy.

IMBRUVICA (ibrutinib)

Manufacturer: Pharmacyclics

Approval Date: April 21, 2020

The FDA expanded the indication of Imbruvica to include the initial treatment of adults with CLL or SLL in combination with rituximab. Approval was based on the E1912 trial, a 2:1 randomized, multicenter, open-label, actively controlled trial. Patients received either ibrutinib with rituximab or fludarabine, cyclophosphamide, and rituximab. The patients, 529 in total, were 70 years of age or younger with previously untreated CLL or SLL requiring systemic therapy. The main efficacy outcome was PFS.

The trial demonstrated a statistically significant improvement in PFS for patients who received ibrutinib and rituximab compared with those who received fludarabine, cyclophosphamide, and rituximab (HR, 0.34; 95% CI, 0.22-0.5; P < .001). The median PFS was not reached after a median follow-up duration of 37 months.

The most common adverse effects were thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, and nausea.

Ibrutinib is administered orally, at a dose of 420 mg, taken once daily with water.

DIAGNOSTIC TESTS/IMAGING

FoundationOne Liquid CDx Test

Manufacturer: Foundation Medicine

Approval Dates: August 26, 2020, October 23, 2020, October 26, 2020, and November 6, 2020

This next-generation sequencing–based test was first approved as a companion diagnostic to identify sequence variations in BRCA1 and BRCA2 genes in cell-free DNA isolated from patients with mCRPC who are eligible for treatment with rucaparib.

The test was then approved as a companion diagnostic to identify fusions in neurotrophic receptor tyrosine kinase genes NTRK1, NRTK2, and NTRK3 in persons with solid tumors eligible for treatment with larotrectinib.

Additional approval was then granted for several indications: (1) to identify mutations in BRCA1 and BRCA2 in persons with ovarian cancer who are eligible for treatment with rucaparib, (2) to identify ALK rearrangements in persons with NSCLC eligible for treatment with alectinib, and (3) to identify mutations in PIK3CA in persons with breast cancer eligible for treatment with alpelisib. Approval was then extended as a companion diagnostic to identify mutations in BRCA1, BRCA2, and ATM in persons with mCRPC eligible for treatment with olaparib.

Approval was based on retrospective testing of available plasma samples. Efficacy was shown to be maintained in patients with confirmed NTRK fusion, BRCA1 and/or BRCA2 alterations, PIK3CA mutations, ALK rearrangement, and BRCA1, BRCA2, and/or ATM alterations.

The FoundationOne Liquid CDx test was granted breakthrough device designation by the FDA.

CERIANNA (fluoroestradiol F 18)

Manufacturer: Zionexa

Approval Date: May 20, 2020

Cerianna is an imaging agent used to visually detect estrogen-receptor (ER)-positive lesions, in combination with a tissue biopsy, in patients with recurrent or metastatic breast cancer. FDA approval was granted based primarily on data from 2 published clinical trials in which patients with recurrent or metastatic ER-positive breast cancer were given Cerianna prior to receiving a positron-emission tomography (PET) scan.

The 2 most common adverse effects of Cerianna are injection site pain and taste change.

Cerianna is injected into the vein prior to a PET scan.

DETECTNET (copper Cu 64 dotatate injection)

Manufacturer: RadioMedix

Approval Date: September 3, 2020

Detectnet is a drug for detection of somatostatin receptor–positive neuroendocrine tumors (NETs) in adults. FDA approval of Detectnet was based on data gathered from 2 trials. The first trial enrolled some people with NETs and some without. All received Detectnet and underwent a PET scan. In the second trial, all the patients had a history of NETs, received Detectnet, and underwent a PET scan. In both trials, Detectnet images were compared with biopsy results or other imaging techniques and interpreted by independent image readers.

Detectnet is injected into the vein prior to a PET scan.

SUPPORTIVE TREATMENT

REBLOZYL (luspatercept-aamt)

Manufacturer: Celgene

Approval Date: April 3, 2020

The FDA granted approval to Reblozyl for the treatment of anemia failing an erythropoiesis-stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Efficacy was demonstrated by the MEDALIST trial, a randomized, multicenter, double-blind placebo-controlled trial. The study included 229 patients with very low-, low-, or intermediate-risk myelodysplastic syndromes with ring sideroblasts and who required RBC transfusions. Patients received either Reblozyl or placebo; all patients received best supportive care. The main outcome end point was the proportion of patients who were RBC-transfusion–independent (absence of any RBC transfusion during 8 consecutive weeks).

Of the 153 patients who received Reblozyl, 58 (95% CI, 30.2-46.1) were RBC-transfusion–independent for at least 8 weeks, whereas only 10 patients (95% CI, 6.5-22.9) in the placebo arm were RBC-transfusion–independent for at least 8 weeks.

The most common adverse effects are fatigue, headache, musculoskeletal pain, arthralgia, dizziness/vertigo, nausea, diarrhea, cough, abdominal pain, dyspnea, and hypersensitivity.

The recommended starting dose of luspatercept-aamt is 1 mg/kg every 3 weeks, administered via subcutaneous injection.