Sahil Doshi, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses retrospective study results, as presented at the 2025 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Results demonstrated that patients who received fewer than 4 doses of ipilimumab and nivolumab due to treatment-related toxicities had overall survival outcomes that were similar to those who had all 4 doses of ipilimumab and nivolumab.

Dr Doshi noted that these results “underscore the importance of continuing to balance treatment efficacy and tolerability when making treatment related decisions.”

Transcript: 

My name is Sahil Doshi, I'm a third-year medical oncology-hematology fellow at Memorial Sloan Kettering Cancer Center and I will be joining the faculty at Memorial Sloan Kettering after my fellowship later this year as a genitourinary medical oncologist with a clinical and research focus on kidney cancer. Earlier this month at the 2025 ASCO GU Symposium, I presented my research on an abstract titled “Outcomes with first-line ipilimumab and nivolumab for patients with metastatic renal cell carcinoma by number of doses.” I'll give an overview of this abstract and our results today. 

Our goal here was to conduct a retrospective, observational analysis to explore Memorial Sloan Kettering Cancer Center's real-world experience with ipilimumab and nivolumab as first-line systemic therapy for patients with advanced renal cell carcinoma. We know that ipilimumab and nivolumab, ipi-nivo for short, are standard, effective first-line systemic therapy options for patients with metastatic disease. The regimen is administered in combination once every 3 weeks for 4 doses, followed by nivo maintenance. In the pivotal Checkmate 214 trial, this regimen was efficacious but was associated with significant toxicity in certain cases as well. The dose and frequency of ipi appears to correlate with treatment safety and tolerability across cancer types and further studies in advanced melanoma have demonstrated that the efficacy of ipi-nivo is largely driven by the first 2 doses in many patients. 

Our primary objective here was to look at the number of ipi-nivo doses that were received by each patient in our cohort and associated survival outcomes. Our methodology involved identifying patients with renal cell carcinoma who had received first-line ipi-nivo as systemic therapy. We looked at the number of doses received of this combination of ipi-nivo: 1, 2, 3, or 4. And if it was fewer than 4 doses, we looked at what those reasons might have been and included reasons such as disease progression prior to completion of the 4 doses or toxicity. We then looked at survival outcomes for patients who received 4 doses versus fewer than 4 doses. We included 222 patients with metastatic renal cell carcinoma that were treated with first-line ipi-nivo in our cohort: 77% of our cohort patients were male, 85% had clear cell disease, and 87% had IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] intermediate or poor risk disease. Of the 222 patients, 145 of them, or 65%, received all 4 doses, 30 patients received 3 doses, 21 received 2 doses, and 26 received 1 dose. The most common reasons for not completing all 4 doses were toxicity and disease progression. All 145 patients who received 4 doses and 44 who received fewer than 4 doses for reasons other than early progression or death were included in our survival analysis. We saw that overall survival in the 4 dose and fewer than 4 dose group at 18 months was comparable, which was 83% in the 4-dose group and 79% in the fewer than 4-dose group, respectively. 

Our main conclusion from this was that the patients who completed all 4 doses of ipi-nivo versus those patients who received fewer than 4 doses of ipi-nivo for reasons that were due to treatment-related toxicity, had overall survival outcomes that were similar between the 2 groups. Thinking about the clinical implications of our findings, our results in this study underscore the importance of continuing to balance treatment efficacy and tolerability when making treatment related decisions and provide clinicians with additional data to guide their decision-making with ipi-nivo in patients with renal cell carcinoma. I believe this data will be especially helpful when clinicians and patients are weighing the potential risks versus benefits of continuing additional ipi-nivo doses versus discontinuing further doses when patients are experiencing borderline higher grade adverse events and toxicity and it's unclear as to whether or not they should continue with additional doses or maybe hold off. I believe the study provides additional data that might guide with that decision-making. 

I do want to underscore that this was a retrospective, observational study and therefore does have some limitations to its conclusions and to really answer the questions whether 4 doses or fewer than 4 doses are sufficient a prospective, randomized trial would be needed to study and understand the non-inferiority of fewer than 4 doses. 

Overall, I believe this study adds to the real-world evidence of tolerability, safety, and efficacy of ipi-nivo in patients with renal cell carcinoma that are starting first-line systemic therapy [and] will provide additional data to guide decision making for clinicians and patients.

Source: 

Doshi S, Sanmiguel AL, Knezevic A, et al. Outcomes with first-line ipilimumab and nivolumab for patients with metastatic renal cell carcinoma by number of doses. Presented at 2025 ASCO Genitourinary Cancers Symposium. February 13-15, 2025; San Francisco, CA. Abstract 540