Robert J. Motzer, MD, on Renal Cell Carcinoma: New Results With Nivolumab and Ipilimumab
ESMO Congress 2022
Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, discusses phase III results of the CheckMate 914 trial, which explored the efficacy of adjuvant nivolumab plus ipilimumab vs placebo in the treatment of patients with localized renal cell carcinoma who are at high risk of relapse after nephrectomy (Abstract LBA4).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The CheckMate 914 trial compared nivolumab plus ipilimumab to placebo in patients who had undergone a nephrectomy for clear cell carcinoma and were at substantial risk of recurrence. The eligibility included patients who were pT2a high grade, any pT2b, any pT3, pT4, or N1 positive disease, and the patients were randomized one to one to Nivolumab, 240 mg IV every two weeks for 12 doses, ipilumumab 1 mg/kg IV every six weeks for four doses or matched placebo. The expected treatment duration of this study was six months. The trial randomized over 800 patients and the patient characteristics were quite balanced. The majority of patients, nearly 80%, fell into the pT3a category. The primary endpoint of the trial was disease-free survival by blind, independent central review, and at the time of the analysis, the trial did not reach the primary endpoint.
The hazard ratio for comparison between the two arms was 0.92, and the P value was 0.53. The 24-month disease-free survival rate was 76% for NIVO plus IPI, and 74% for placebo. The adverse event profile for NIVO plus IPI was similar to that, which we had seen in the studying of advanced disease. However, few patients, relatively few, completed the full 12 courses of NIVO and four of IPI, only 57%. The proportion of patients that had treatment-related grade three or higher AEs was 28% for NIVO plus IPI, compared to 2% per placebo. This is actually a lower rate than we saw for NIVO plus IPI in the setting of metastatic disease, but the treatment discontinuation rate was relatively high in this trial in the adjuvant setting. Treatment adverse events were as expected. The most common was pruritus, fatigue, and diarrhea, as we'd expect for NIVO plus IPI, and the proportion of patients who required high dose steroids on this NIVO plus IPI program was 23%.
In summary then, part A of CheckMate 914 trial, which compares NIVO plus IPI to placebo in patients with localized RCC at high risk of post-nephrectomy relapse did not meet the primary endpoint of disease-free survival. The safety profile of NIVO plus IPI was consistent with the known profile for the combination of advanced RCC. However, the rate of discontinuation due to treatment-related adverse events was considerable with NIVO plus IPI in the adjuvant setting. Further analysis underway to understand the outcome of CheckMate 914 with regard to the patient population studied, and there is a part B, which is essentially a separate trial that has a primary endpoint of comparing NIVO monotherapy to placebo. That study is ongoing.
Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute, and Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discuss results from two important trials presented at ESMO 2022: Cohort 1 of the LITESPARK-003 study of belzutifan plus cabozantinib as first-line treatment of advanced renal cell carcinoma (RCC), and the KEYNOTE-B61 study of pembrolizumab plus lenvatinib as first-line treatment for non–clear cell RCC (Abstracts 1447O and 1448O).
Neal D. Shore, MD, of Carolina Urologic Research Center/Genesis Care, discusses new data from the ENACT trial, which showed that patients with prostate cancer and the RNA biomarkers PAM50 and AR-A were likely to have better outcomes with enzalutamide treatment. The results suggest that such RNA biomarkers may help to identify patients who may benefit from enzalutamide treatment compared with active surveillance (Abstract 1385P).
Christelle de la Fouchardiere, MD, of France’s Centre Léon Bérard, discusses phase III findings from the PRODIGE 65–UCGI 36–GEMPAX UNICANCER study, which evaluated whether the combination of gemcitabine and paclitaxel improves overall survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma after FOLFIRINOX failure or intolerance (Abstract LBA60).
Rahul Aggarwal, MD, of the University of California, San Francisco, discusses recent data from the PRESTO study, which showed that apalutamide plus androgen-deprivation therapy (ADT) for 12 months significantly prolonged PSA progression-free survival compared with ADT alone in patients with biochemically recurrent prostate cancer. These results provide support for the intensification of ADT in this setting. (Abstract LBA63).
Matthew P. Goetz, MD, of Mayo Clinic, discusses recent data from the MONARCH 3 trial of patients with advanced hormone receptor–positive, HER2-negative breast cancer. The study, a second interim analysis, showed that longer overall survival was observed in both the intention-to-treat group as well as in the subgroup with visceral disease. However, neither met the threshold for statistical significance, and further analyses are planned when more data can be reported. (Abstract LBA15).