In this interview, Sahil Doshi, MD, discusses the outcomes of a recent trial he authored on first-line ipilimumab and nivolumab for metastatic renal cell carcinoma, highlighting its implications for clinical practice and payer considerations.

Sahil Doshi, MD: I'm Sahil Doshi, MD. I'm a third-year medical oncology hematology fellow at Memorial Sloan Kettering Cancer Center. Over the last 2 years, during my fellowship years, I've had a clinical and research focus in genitourinary oncology with a specific focus in renal cell carcinoma (RCC), both in clinical research and clinical trials.

What were the primary objectives and key endpoints of the trial?

Dr Doshi: 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. Our primary objective was to look at the number of ipilimumab and nivolumab (ipi + nivo) doses that were received by each patient in our cohort, those doses ranging from 1 through 4, and then associated survival outcomes.

What are your key takeaways from the similar overall survival (OS) rates between patients who completed 4 doses and those who received fewer doses due to toxicity?

Dr Doshi: Essentially what we did is we took all the patients in our cohort (n = 222) and we divided them by the number of ipilimumab and nivolumab doses that were received—either 1, 2, 3, or 4. If it was fewer than 4 doses, we looked at what those reasons might have been, and included things such as disease progression prior to completion of the 4 doses or toxicity. Then we looked at survival probabilities and survival outcomes for patients who received 4 doses vs fewer than 4 doses.

Our main conclusion was that the patients who completed all 4 doses vs those patients who received fewer than 4 doses for reasons due to treatment-related toxicity had overall some survival outcomes that were similar between the two groups.

How did these results inform our understanding of the balance between treatment tolerability and efficacy with ipi + nivo and RCC?

Dr Doshi: That's a great question. That was really what we were trying to understand better, and really seeing, with toxicity, what the outcomes are like. We know that ipilimumab and nivolumab is an effective treatment regimen for patients with advanced renal cell carcinoma, but we also know that this treatment regimen can be toxic to patients.

In the pivotal CheckMate 214 trial, ipilimumab and nivolumab was shown to be more effective than sunitinib, but it did have associated treatment-related adverse events. In this study, nearly all patients experienced treatment-related adverse events of any grade, and almost half experienced grade 3 to 4 treatment-related adverse events.

This was lower, though, than those patients who received sunitinib, and so this regimen was concluded to be both more efficacious and tolerable than sunitinib. 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.

I believe this data will be especially helpful when clinicians and patients are weighing the potential risks vs benefits of continuing additional ipilimumab and nivolumab doses vs discontinuing further doses when patients are experiencing borderline higher-grade adverse events and it's more unclear as to what to do. This study just provides additional data that might help with that decision-making.

For patients who experience toxicity, do these findings support a potential change in clinical practice, such as adjusting the number of planned ipi + nivo doses?

Dr Doshi: While we did find comparable overall survival in patients who received the 4 doses compared to those who received fewer than 4 doses for primarily toxicity-related reasons, I do want to underscore that this was a retrospective observational study and therefore has limitations to its conclusions.

I don't believe these findings alone support a potential change in clinical practice, but they do suggest that there is some similarity for patients who experience toxicity and that it might be okay to do fewer than 4 doses if it's needed. But I think to really answer that question, a prospective randomized trial would be needed to study and understand the noninferiority of fewer than 4 doses.

How do your findings contribute to the broader body of evidence regarding immune checkpoint inhibitors in RCC and other cancers?

Dr Doshi: Our main takeaway here was really that we did see comparable overall survival probabilities in those patients who received all 4 doses of ipilimumab plus nivolumab compared to those who received fewer than 4 doses.

This adds to the real-world evidence for patients outside of clinical trials as to how they're tolerating ipilimumab plus nivolumab and how many patients are able to go through all 4 doses vs not receive all 4 doses. It just gives more data to guide clinical decision-making.

The goal of this was really to better understand what is happening to those patients who receive fewer than 4 doses. What does their overall survival look like compared to those that actually are able to make it through all 4 doses? Here, I think, it was reassuring to see that the ones who discontinue for toxicity are doing similarly. But in terms of changing clinical practice or making bigger statements, we would really need larger studies that are more prospective in nature to answer those types of questions.