Recent News About the Expanding Landscape of Treatments for Breast Cancer

The American Cancer Society (ACS) estimates that approximately 281,550 women will receive a diagnosis of invasive breast cancer in 2021.¹ The ACS also notes that in 2021 an estimated 49,290 new cases of ductal carcinoma in situ will be diagnosed and an estimated 43,600 women will die as a result.¹ Due to increased awareness and advances in screening, treatment, and management, mortality rates from breast cancer diminished by 40% between 1989 and 2017 which equates to 375,900 deaths averted within that time frame.²

Innovations in treatments and ongoing research efforts for breast cancer provides clinicians and patients battling breast cancer with an expanding landscape of treatment options that may improve overall clinical outcomes and decrease mortality rates.

In a recent interview posted on the website, Survivornet.com, Dr Elizabet Comen, a medical oncologist at Memorial Sloan Kettering Cancer Center stated, “For women who’ve been diagnosed with breast cancer, the advancements of the last year represent increased options. As you learn very quickly when you’re diagnosed, breast cancer is actually many different diseases depending on the hormones driving your cancer and the molecular and genetic makeup of your specific disease. Despite the pandemic, there have still been considerable advances in breast cancer in the past two years.” ³

Dr Comen also added, “These advancements give us the ability to keep fighting for women every day. Talk to your doctor. Make sure you understand what type of breast cancer you have and if any of these newer therapies may be right for you.”³

Various news stories have revealed that the use of pharmacological agents such as immunotherapy, the poly adenosine diphosphate-ribose polymerase inhibitors (PARP inhibitors), and antibody drug conjugates are demonstrating promising clinical data and may have a positive impact in the treatment of various types of breast cancer including early-stage BRCA1/2 breast cancer, triple-negative breast cancer and advanced breast cancer. Below is a summary of some recent news stories about breast cancer research and treatments:

• On October 4, 2021, the FDA granted the HER2 directed antibody drug conjugate, Enhertu® (fam-trastuzumab deruxtecan-nxki) Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens. The FDA granted BTD based on data from the DESTINY-Breast03 pivotal trial presented during the 2021 European Society for Medical Oncology (ESMO) Congress. In the trial, fam-trastuzumab deruxtecan-nxki demonstrated a 72% reduction in the risk of disease progression or mortality compared to T-DM1 (hazard ratio [HR] = 0.28; 95% CI: 0.22-0.37; p=7.8x10-22) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.⁴ The safety profile of the most common adverse events with fam-trastuzumab deruxtecan-nxki in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified.⁴
• A presentation at the ESMO Congress 2021 indicated that according to results from the Phase 3 MONALEESA-2 trial, adding the kinase inhibitor, ribociclib to first-line letrozole improves overall survival (OS) by more than 1 year in postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer.⁵ The presenter indicated that this is the longest median survival reported to date in any advanced breast cancer phase 3 clinical trial.^5,6
• In July 2021, the FDA approved anti-programmed death receptor-1 (PD-1) therapy, pembrolizumab (Keytruda) for high-risk, early-stage, triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery based on findings from the Phase 3 KEYNOTE-522.⁷ In September 2021, the manufacturer announced the final overall survival (OS) results from the pivotal Phase 3 KEYNOTE-355 trial investigating pembrolizumab in combination with chemotherapy (paclitaxel, nab-paclitaxel or gemcitabine/carboplatin) for the first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC). In this study, the use of pembrolizumab plus chemotherapy diminished the risk of death by 27% versus chemotherapy as first line treatment for patients with mTNBC whose tumors expressed PD-L1 (Combined Positive Score [CPS] ≥10), as compared to chemotherapy alone. There was an increase of 6.9 months in median OS with pembrolizumab plus chemotherapy compared to chemotherapy alone (23.0 months [95% CI, 19.0-26.3] vs. 16.1 months [95% CI, 12.6-18.8], respectively).^7,8 Pembrolizumab is the first anti-PD-1 therapy in combination with chemotherapy to demonstrate a statistically significant and clinically meaningful improvement in OS for these patients. These findings were presented at the ESMO Congress 2021.
• Data was recently presented on the use of the PARP inhibitor, Lynparza (olaparib) following standard-of-care treatments—including surgery, chemotherapy, hormone therapy or radiation therapy, in patients with BRCA1/2-mutant, early HER2-negative breast cancer who are at high risk for disease recurrence.⁹  Findings from the phase 3 OlympiA trial indicated that after a median follow-up of 2.5 years, patients who received olaparib experienced a 42% reduction in invasive disease-free survival, including local and metastatic recurrence of breast cancer, other new cancers, and death due to any cause.^9,10
• Data from a Phase 2 trial NEOTALA which involved 61 patients exploring the use of another PARP inhibitor, Talzenna (talazoparib) for the treatment of patients with germline BRCA1/2 mutation-positive, HER2-negative breast cancer before undergoing breast surgery revealed that an estimated 50% of patients who received talazoparib before surgery had a complete response (disappearance of all signs of cancer) to treatment.⁹ In a statement on the Cure Magazine website, Dr. Melinda Telli, an associate professor of medicine at Stanford University School of Medicine in California and director of the breast cancer program at Stanford Cancer Institute stated, “That is around the type of complete response rate that we typically see with combination chemotherapy for triple-negative breast cancer with a BRCA1/2 mutation, so I think this is really provocative data.” She added, “The hope is that these approaches will continue to be studied to see if this could be an option for more patients in the future, a chemotherapy-free treatment regimen,” ⁹

The promising clinical data mentioned above provides clinicians who treat patients with breast cancer and the patients battling breast cancer with a ray of hope and ongoing research efforts will continue to shed more light on understanding the best approaches for the detection, treatment, and prevention of breast cancer.  While October is Breast Cancer Awareness month, let’s make every day, a day to bring attention to the significance of early detection, screenings, preventative measures, and prompt initiation of therapy to improve clinical outcomes for breast cancer. There are several studies listed on the US National Library of Medicine’s Clinical Trials.gov website and maybe one day, researchers will find a cure. 

Disclaimer: The views and opinions expressed are those of the author(s) and do not necessarily reflect the official policy or position of the Population Health Learning Network or HMP Global, their employees, and affiliates. Any content provided by our bloggers or authors are of their opinion and are not intended to malign any religion, ethnic group, club, association, organization, company, individual, or anyone or anything.

References

1. How Common Is Breast Cancer? American Cancer Society website. https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html  Revised May 7,  2021. Accessed October 7, 2021.
2. Report: Breast Cancer Death Rates Down 40% Since 1989. American Cancer Society website. https://www.cancer.org/latest-news/report-breast-cancer-death-rates-down-40-percent-since-1989.html  Published October 2, 2019. Accessed October 7, 2021.
3. Schaefer S. It’s National Breast Cancer Awareness Month; Here Are Four Treatment & Screening Advancements Women Should Know. Survirnet.com https://www.survivornet.com/articles/breast-cancer-treatment-screening-advancements-2021/ Published October 6, 2021. Accessed October 7, 2021.
4. ENHERTU® Granted Breakthrough Therapy Designation in U.S. for Patients with HER2 Positive Metastatic Breast Cancer Treated with One or More Prior Anti-HER2-Based Regimens. Business Wire.com. https://www.businesswire.com/news/home/20211003005046/en/ENHERTU%C2%AE-Granted-Breakthrough-Therapy-Designation-in-U.S.-for-Patients-with-HER2-Positive-Metastatic-Breast-Cancer-Treated-with-One-or-More-Prior-Anti-HER2-Based-Regimens Published October 4, 2021. Accessed October 7, 2021.
5. Hortobagyi GN, Stemmer SM, Burris, HA, et al. Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor 2 negative (HR-positive/HER2-negative) advanced breast cancer (ABC) treated with endocrine therapy (ET) +/- ribociclib (RIB). Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. LBA17_PR.
6. Fuerst M. Ribociclib Improves Survival by More Than 1 Year in Advanced Breast Cancer. Clinical Therapy Advisor website. https://www.cancertherapyadvisor.com/home/news/conference-coverage/esmo-2021/breast-cancer-ribociclib-improves-survival-treatment-risk/  Published September 20,2021. Accessed October 7, 2021. 
7. Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Reduced Risk of Death by 27% Versus Chemotherapy as First-Line Treatment for Patients With Metastatic Triple-Negative Breast Cancer Whose Tumors Expressed PD-L1 (CPS ≥10).Business Wire.com https://www.businesswire.com/news/home/20210919005025/en/Merck%E2%80%99s-KEYTRUDA%C2%AE-pembrolizumab-Plus-Chemotherapy-Reduced-Risk-of-Death-by-27-Versus-Chemotherapy-as-First-Line-Treatment-for-Patients-With-Metastatic-Triple-Negative-Breast-Cancer-Whose-Tumors-Expressed-PD-L1-CPS-%E2%89%A510 Published September 19, 2021. Accessed October 7, 2021.
8. Rugo HS, et al. Abstract LBA16. Presented at: European Society for Medical Oncology Congress (virtual meeting); Sept. 17-21, 2021.
9. Dobkowski D. New Treatments in Breast Cancer May Lead to Less Toxicity, Improved Response Rates. Cure.com. https://www.curetoday.com/view/new-treatments-in-breast-cancer-may-lead-to-less-toxicity-improved-response-rates Published October 4, 2021. Accessed October 7, 2021. 
10. Marabella C. Lynparza Following Standard of Care Treatments Effective in Some Patients with High-Risk Breast Cancer. Cure.com https://www.curetoday.com/view/lynparza-following-standard-of-care-treatments-effective-in-some-patients-with-high-risk-breast-cancer  Publsihed June 5, 2021. Accessed October 8, 2021.