Michael B. Atkins, MD, on Renal Cell Carcinoma: Phase II Findings on Nivolumab and Ipilimumab
2023 ASCO Genitourinary Cancers Symposium
Michael B. Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, discusses treatment-free survival outcomes from the HCRN GU16-260-Cohort A study of patients with previously untreated advanced clear cell renal cell carcinoma who received nivolumab and salvage nivolumab plus ipilimumab. The regimen appears to result in substantial treatment-free survival with few treatment-related adverse events. (Abstract 604).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
This trial was a trial of nivo monotherapy followed by nivo/ipi boost for patients with treatment-naive clear cell metastatic kidney cancer. And we knew that immunotherapy can produce durable benefit even after treatment cessation, and also have some toxicities that occur after treatment cessation. And so we devised an endpoint called treatment-free survival that could characterize that period of time after treatment stops. And we've looked at this in patients with melanoma and kidney cancer on other trials, but those trials were flawed because the only reason why patients stopped was for toxicity or for disease progression, and there wasn't a built-in treatment endpoint.
In the HCRN GU16-260 trial, there was a endpoint of treatment at 96 weeks, and so that gave us an opportunity to look at treatment-free survival in a situation where treatment stopped. And we looked at the data, now 37.7 months of follow-up and 128 patients were enrolled. And we looked at part A, which was nivo, and for the people who got nivo/ipi boost, part B, we looked at that as one regimen. And with that, and we looked at a 36 month period of time, and we defined treatment-free survival as the area between the registration and time to be getting a second therapy, and the time from registration and the time to stopping the first therapy.
First of all, we saw that the response rate was 36%, 58% in the favorable risk population, and 27% in the intermediate and poor risk population, and that 68% of patients were alive at that three-year time point. And 38% of those patients who were alive were treatment free. But looking at that treatment-free survival on the graph, we saw that for the whole population, treatment-free survival was about 9.5 months. Overall survival average was 30 months, and 11.5 months on treatment and nine months on subsequent treatment. So treatment-free survival represented somewhere around a 36% of the total time. And in the favorable risk population, treatment-free survival was longer at 12.9 months. And in the intermediate poor risk population, it was shorter, around eight months and about 22% of that total time.
But in each of those cases, it was longer than the treatment-free survival in the CheckMate 214 trial for the ipi/nivo arm showing the benefit of actually having a treatment cessation endpoint. So we concluded that treatment-free survival is an interesting endpoint for immunotherapy trials, gives information that is not captured with traditional endpoints, and having a trial with stopping therapy shows better the value of treatment-free survival. And it's something that should be potentially considered as a endpoint that patients care about for future trials. And then another thing, it continues to show in this trial how well the favorable risk population does with immune therapy, and argues for having a pure immune therapy in the favorable risk population.
Aristotelis Bamias, MD, of the National and Kapodistrian University of Athens, discusses results from the phase III IMvigor130 study, which suggest that atezolizumab monotherapy continues to show better tolerability vs chemotherapy for patients with untreated locally advanced or metastatic urothelial carcinoma. (Abstract LBA441).
Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, discusses new data from the COSMIC-313 study of patients with advanced renal cell carcinoma of IMDC (International Metastatic RCC Database Consortium) intermediate or poor risk. Those who received cabozantinib instead of placebo with nivolumab and ipilimumab as first-line treatment seemed to experience improved progression-free survival. A subgroup analysis suggested the benefit was primarily in patients with an intermediate risk. Follow-up for overall survival is ongoing. (Abstract 605).
Alan H. Bryce, MD, of the Mayo Clinic, discusses the final results of the primary endpoint of rPFS and interim results on overall survival among patients with chemotherapy-naive metastatic castration-resistant prostate cancer. The data showed that rucaparib improved radiographic progression-free survival compared with either docetaxel or abiraterone and enzalutamide in disease with BRCA1/2 alterations. (Abstract 18).
Scott T. Tagawa, MD, of Weill Cornell Medicine, NewYork-Presbyterian Hospital, discusses study results showing that, the anti-PSMA (prostate-specific membrane antigen) monoclonal antibody J591 with ketoconazole and hydrocortisone, when radiolabeled with lutetium-177, leads to improved 18-month metastasis-free survival vs radiolabeling with indium-111 in patients with nonmetastatic (M0) castration-resistant prostate cancer. This supports the development of anti-PSMA radioimmunotherapy, although the optimal radionuclide and targeting agent are unknown. (Abstract LBA21).
Daniel P. Petrylak, MD, of the Yale Cancer Center, discusses a primary phase II analysis of the TROPHY-U-01 study, cohort 2, which evaluated sacituzumab govitecan-hziy in platinum-ineligible patients with metastatic urothelial cancer that progressed after prior checkpoint inhibitor therapy. (Abstract 520).