The European Society of Medical Oncology (ESMO) is the leading professional organization for medical oncology in Europe, with more than 23,000 members representing oncology professionals from over 150 countries worldwide. Founded in 1975, ESMO welcomes oncology professionals from around the world and works to bring together professionals with diverse expertise and experience. ESMO aims to foster integrated cancer care by supporting oncologists in their professional development and advocating for sustainable cancer care worldwide.
The ESMO Annual Congress was held September 26-30, 2019 in Barcelona, Spain. Journal of Clinical Pathways was on site to provide coverage of the most relevant and important sessions of the meeting.
Additional presentation coverage and interviews can be found online here.
Radiotherapy After Surgery Deemed Unnecessary for Patients With Prostate Cancer
A study presented at the ESMO Annual Congress shed new light on the debate over the benefits of radiotherapy after surgery for prostate cancer.
Chris Parker, MD, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research (London, UK), presented the results of the RADICALS-RT trial, which enrolled 1396 patients after surgery for prostate cancer. Patients were sampled from the UK, Denmark, Canada, and Ireland and were randomly assigned to treatment arms that included postoperative radiotherapy or observation only.
After a median follow-up of 5 years, Dr Parker reported that progression-free survival was 85% in the radiotherapy group compared with 88% in the standard-of-care group (hazard ratio [HR], 1.10; 95% CI, 0.81-1.49; P = .56).
Dr Parker and colleagues acknowledged that self-reported urinary incontinence was slightly higher in patients receiving radiotherapy compared with those receiving standard-of-care therapy (5.3% vs 2.7%, respectively). Nonetheless, he stated that longer follow-up is needed to report on survival and on freedom from distant metastases.
These findings were confirmed in a collaborative meta-analysis presented immediately after Dr Parker’s presentation. Claire Vale, MD, MRC Clinical Trials Unit, University College London (UK), and colleagues combined the results of RADICALS-RT with two similar trials: RAVES and GETUG-AFU17. The ARTISTIC meta-analysis was planned before the results of the trials were known, Dr Vale noted.
Results were based on the 2151 patients included in the three trials, of whom 1074 were randomized to receive adjuvant radiotherapy and 1077 of whom received early salvage radiotherapy. The analysis did not find evidence that adjuvant radiotherapy improves event-free survival compared with early salvage radiotherapy (HR, 1.09; 95% CI, 0.86-1.39; P=.47).
“Results of the ARTISTIC meta-analysis confirm those of RADICALS-RT and provide greater evidence to support the routine use of observation and early salvage radiotherapy,” Dr Vale stated in her presentation. “The meta-analysis provides the best opportunity to assess whether adjuvant radiotherapy may still have a role in some groups of men, and to investigate longer-term outcomes.”
AI Combining Radiomics, Clinical Data Predicts Response to Immunotherapy
A computed tomography (CT) radiomics signature designed by researchers at the Vall d’Hebron Institute of Oncology (VHIO; Barcelona, Spain) is able to predict response to immune checkpoint inhibitors at baseline for patients with solid tumors.
Currently, there are limited indicators to determine response to immunotherapy in oncology. Novel computational analysis of CT scans, such as radiomics, provides information about tumor-infiltrating CD8 and may provide an accurate prediction of response to immunotherapy.
Marta Ligero, MD, Radiomics Group, VHIO, presented at the ESMO Annual Congress on a study aimed to validate the VHIO CT-radiomics signature in an external cohort. Dr Ligero and colleagues also sought to develop a combined radiomics-clinical signature that is able to predict the response to immune checkpoint inhibitors in patients with advanced solid tumors.
The signature was developed in a population of 155 patients treated with single-agent PD-1 or PD-L1 inhibitors in phase 1 clinical trials (cohort 1). Researchers also formed an external validation cohort consisting of 62 patients with urinary bladder cancer treated with single-agent PD-1 or PD-L1 therapy (cohort 2).
Dr Ligero and colleagues delineated a target lesion per patient from the baseline CT scan and extracted radiomic variables, including first-order, shape, and texture. An elastic-net model combining radiomics and clinical features was implemented.
The CT-radiomics signature was associated with an area under the curve of 0.81 and 0.76 in cohort 1 and cohort 2, respectively. The model combining radiomics and clinical features had an area under the curve of 0.84 for response prediction.
Additionally, Dr Ligero reported that tumor homogeneity, hypodensity, spherical shape, high lymphocytes, and low neutrophils corresponded with a high clinical-radiomics signature score.
The VHIO CT-radiomics signature is a potential noninvasive, cost-effective biomarker for patients with advanced solid tumors, Dr Ligero concluded in her presentation. Large-scale prospective datasets for further clinical implementation are needed to validate the signature,
she noted.
Meaningful Clinical Benefit Reported From First-Line Immunotherapy in Advanced Hepatocellular Carcinoma
The CheckMate 459 study may not have reached its predetermined primary endpoint for improved overall survival (OS), but it did show improved OS and response rates in patients with advanced hepatocellular carcinoma (HCC) treated with first-line nivolumab compared with sorafenib.
Results of the study were presented by lead author Thomas Yau, MD, University of Hong Kong (China) at the ESMO Annual Congress.
Dr Yau and colleagues conducted a phase 3 study to compare the clinical efficacy and safety of nivolumab vs sorafenib as first-line therapy options in patients with advanced HCC. Patients were randomized 1:1 (nivolumab, 371 patients; sorafenib, 372 patients). The primary endpoint was OS, and secondary endpoints included objective response rate (ORR) and progression-free survival (PFS). Researchers also assessed for PD-L1 expression and safety.
After a minimum follow-up of 22.8 months, researchers found that OS did not meet the predefined threshold of statistical. However, median OS was 16.4 months for patients receiving nivolumab compared with 14.7 months for those receiving sorafenib. Similarly, ORR was 15% and 7%, respectively, in the treatment arms.
Grade 3/4 treatment-related adverse events were reported in 22% of patients in the nivolumab arm and in 49% of patients in the sorafenib arm. Dr Yau noted that no new safety signals were observed with nivolumab.
“These results are important in the treatment of HCC, as there have been no significant advances over sorafenib in the first-line setting in more than a decade,” stated Dr Yau. “The encouraging efficacy and favorable safety profile seen with nivolumab demonstrates the potential benefit of immunotherapy as a first-line treatment for patients with this aggressive cancer.”
Furthermore, he added that the patient-reported findings suggest that patients in the nivolumab arm experienced better quality of life and further supported clinical data that demonstrated a treatment benefit for nivolumab in this population.
Prognostic Factors After Stem Cell Transplant, Therapy for Hodgkin Lymphoma
Brentuximab vedotin improves the therapeutic response and prolongs progression-free survival (PFS) in patients with Hodgkin lymphoma with a previous bad prognosis, according to a study presented at the ESMO Annual Congress.
Prior research has demonstrated that brentuximab vedotin has helped improve the prognosis and survival of patients with Hodgkin lymphoma who had relapsed after stem cell transplantation or had refractory disease.
Veselina Goranova-Marinova, MD, PhD, clinical hematology, Medical University Plovdiv (Bulgaria), and colleagues designed a study to analyze the prognostic factors influencing outcomes after therapy with brentuximab vedotin in relapsed or refractory patients with Hodgkin lymphoma. A total of 64 patients treated with brentuximab vedotin in six hematology clinics in Bulgaria were included in the study.
Patients received a median of four treatment lines before brentuximab vedotin and 46.9% (n=30) received at least three treatment lines. Autologous stem cell transplantation (ASCT) was performed in 70.3% (n=45) of patients.
Results of the analysis showed that the overall response rate was 60.9% (n=39) after therapy. Stable disease was registered in 10.9% (n=7) and progression was observed in 28.1% (n=18).
PFS for the patient population was 14 months. Median survival was not reached by the end of the analysis. Partial therapeutic response or better was significantly higher in patients with chemotherapy-sensitive disease before ASCT, those who underwent ASCT, and those who started brentuximab vedotin as consolidation therapy within 3 months of ASCT.
Researchers also noted that the only significant prognostic factor that determined a substantially longer event-free survival was the type of therapeutic response; for patients with a complete or partial response to therapy, the median PFS was not reached by the end of the analysis, but patients with stable disease or progression had an event-free survival of 7 months.
Authors of the study concluded that brentuximab vedotin is most effective in patients with chemotherapy-sensitive disease and when used as a consolidation therapy immediately after ASCT. “Brentuximab vedotin improved the therapeutic response and prolongs PFS in patients with Hodgkin lymphoma who previously had really bad prognosis,” they wrote.
Addition of PARP Inhibitor to Front-Line Chemo, Maintenance in High-Grade Ovarian Cancer
A recent phase 3 study assessed the impact on PFS of integrating veliparib to front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin. Results of the study were presented at the ESMO Annual Congress.
Robert L Coleman, MD, The University of Texas MD Anderson Cancer Center (Houston, TX), and colleagues designed a phase 3 study to evaluate whether PFS is increased when veliparib is added to front-line carboplatin and paclitaxel and continued as maintenance therapy in newly diagnosed high grade serous carcinoma. Considerations of BRCA mutations, homologous recombination deficiency (HRD), and neoadjuvant chemotherapy utilization were included in the study.
A total of 1140 previously untreated patients with stage III-IV disease were treated with six cycles of carboplatin plus paclitaxel following primary cytoreduction or neoadjuvant chemotherapy with interval cytoreduction. Veliparib or placebo was administered during front-line therapy and as maintenance. Patients were randomized (1:1:1) to three treatment arms: chemotherapy plus placebo then placebo maintenance (Arm 1); chemotherapy plus veliparib then placebo maintenance (Arm 2); and chemotherapy plus veliparib then veliparib maintenance (Arm 3).
The primary endpoints included PFS in Arm 3 vs Arm 1 using hierarchical testing in BRCA mutations, HRD, and whole populations. Secondary endpoints included PFS in Arm 2 vs Arm 1, overall survival, and disease-related symptom scores.
Among the total patient population, 26% had BRCA mutations and 55% had HRD. Dr Coleman and colleagues found that veliparib added to front-line chemotherapy and continued as monotherapy (Arm 3) significantly extended PFS in all patients, regardless of BRCA or HRD status. The median PFS was 23.5 months in Arm 3 vs 17.3 months in Arm 1 (HR, 0.68; 95% CI, 0.56-0.83; P<.001).
Furthermore, grade 3/4 adverse events were similar during chemotherapy in Arm 3 compared with Arm 1, though were higher for veliparib treatment during maintenance. Nonetheless, serious adverse events were similar between the treatment arms during maintenance. The observed toxicities were consistent with the known safety profile of veliparib, Dr Coleman added.
Study findings were published in the New England Journal of Medicine at the time of his presentation (online September 28, 2019; doi:10.1056/NEJMoa1909707).
Apalutamide Reduces Risk of Death in Patients With Nonmetastatic Castration-Resistant Prostate Cancer
Results from a second interim analysis for OS from the phase 3 SPARTAN study, presented at the ESMO Annual Congress, show apalutamide is associated with a 25% reduction in the risk of death compared with placebo in patients with nonmetastatic castration-resistant prostate cancer (CRPC).
The phase 3 SPARTAN study evaluated the addition of apalutamide or placebo to androgen deprivation therapy in men with high-risk nonmetastatic CRPC. A total of 1207 patients were randomized 2:1 to either apalutamide or placebo.
“As previously reported, apalutamide significantly improved median metastases-free survival by more than 2 years and reduced the risk of metastases or death by 72%. Apalutamide also significantly improved time to symptomatic progression,” explained Matthew Smith, MD, PhD, Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center and Harvard Medical School (Boston, MA), during his presentation.
Because of this, the study was unblinded and apalutamide was offered to patients on placebo. A total of 76 patients who did no progress on placebo crossed over to open-label apalutamide.
“At the primary analysis for MFS, the survival data were immature, with only 104 of 427 events (24%) required for the prespecified final OS analysis,” Dr Smith added.
At 41 months median follow-up and 285 events, Dr Smith and colleagues conducted a second interim analysis for OS. At the time of the second interim analysis, apalutamide was associated with improved OS compared with placebo HR, 0.75; 95% CI, 0.59-0.96; P=.0197). The 4-year OS rates for apalutamide and placebo were 72.1% and 64.7%, respectively.
At the second interim analysis, 68% of patients in the placebo group and 38% of patients in the apalutamide group received subsequent life-prolonging therapy.
The median treatment duration for apalutamide was 31.4 months compared to 11.5 months for placebo. Discontinuation rates due to progressive disease of adverse events (AEs) were 34% and 14%, respectively, in the apalutamide arm and 74% and 8%, respectively, in the placebo arm. Treatment-related AEs were similar to rates reported at the first interim analysis.
“In summary, apalutamide is associated with 25% reduction in risk of death compared to placebo; this OS benefit for apalutamide was observed despite crossover of placebo patients to apalutamide and higher rates of subsequent life-prolonging therapy than the placebo group,” said Dr Smith, adding that the OS improved was consistent across subgroups and the apalutamide safety profile remains unchanged with further follow-up.
“Collectively these results provide further support for apalutamide as a standard-of-care option for men with high-risk nonmetastatic CRPC,” Dr Smith concluded.
Niraparib Associated With Longer PFS in Newly Diagnosed Ovarian Cancer
Niraparib is associated with significantly longer PFS than placebo among patients with newly diagnosed advanced ovarian cancer, according to results from the phase 3 PRIMA study.
These results were presented by Antonio Gonzalez-Martin, MD, co-director, department of medical oncology, Clinica Universidad de Navarra (Spain), at the ESMO Annual Congress.
PRIMA randomized patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy.
The primary endpoint was PFS in patients whose tumors had homologous-recombination deficiency as well as PFS in the overall population. A prespecified interim analysis for OS was conducted at the time of the primary analysis for PFS.
A total of 733 patients underwent randomization. Of these patients, 373 (50.9%) had homologous-recombination deficient tumors.
The median PFS among patients with homologous-recombination deficient tumors was significantly longer in those who received niraparib than those who received placebo (21.9 months vs 10.4 months; HR, 0.43; 95% CI, 0.31-0.59; P<.001).
In the overall population, the median PFS was 13.8 months with niraparib compared with 8.2 months with placebo (HR, 0.62; 95% CI, 0.50-0.76; P<.001)
The rate of OS at the 24-month interim analysis was 84% in the niraparib group compared with 77% in the placebo group (HR, 0.70; 95% CI, 0.44-1.11).
The most common adverse events grade ≥3, occurring in 31% of patients, were thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths were reported.
“Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency,” Dr Gonzalez-Martin and colleagues reported.
“Based on these results, niraparib monotherapy after first-line platinum-based chemotherapy should be considered a new standard of care,” Dr Gonzalez-Martin concluded during his presentation.
Additional presentation coverage and interviews can be found online here.
