The immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy) was associated with an increase in treatment-free survival (TFS) versus sunitinib (Sutent) in patients with advanced renal cell carcinoma (RCC), according to a retrospective analysis of the phase 3 CheckMate-214 trial published in Clinical Cancer Research.1,2
At 42 months’ follow-up the analysis showed a nearly threefold improvement in mean TFS among favorable-risk patients receiving nivolumab/ipilimumab: 11.0 months versus 3.7 months with sunitinib. The mean TFS in intermediate/poor-risk patients was also improved at 6.9 versus 3.1 months, respectively.
“One of the great challenges in conducting clinical trials is that some of the endpoints we’ve been using to measure the efficacy and value of a treatment are not optimal, especially when evaluating immuno-oncology-based therapy regimens,” first study author Meredith Regan, ScD, explained in a news release.“As we continue to develop new treatments, we have an opportunity to think about new methods to better balance the efficacy and toxicity to the patients. To do that, we needed a new endpoint to quantify those two aspects together—to continue to improve survival for patients while also focusing on how they are spending their time. That’s how TFS came to be,” added Regan, an associate professor at Harvard Medical School and Dana-Farber Cancer Institute.
In the retrospective study, investigators analyzed data of 550 patients who received the checkpoint inhibitor combination and 546 patients who received sunitinib. All patients had not undergone any treatment for advanced renal cell carcinoma prior to the CheckMate-214 trial and were randomized 1:1 to receive either treatment.
If patients were randomized to immunotherapy, they received 3 mg/kg of nivolumab and 1 mg/kg of ipilimumab intravenously every 3 weeks for 4 doses followed by 3 mg/kg of nivolumab every 2 weeks. If patients were randomized to targeted therapy, they received 50 mg of sunitinib orally once daily for 4 weeks of every 6-week cycle. Treatment continued until progressive disease or unacceptable toxicity.
Findings indicated that 52% of intermediate/poor-risk patients who received nivolumab plus ipilimumab were alive at 42 months, versus 39% who received sunitinib. Of these patients, 18% and 5% survived treatment-free, respectively. Seventy percent of favorable-risk patients who received nivolumab plus ipilimumab were alive at 42 months, versus 73% who received sunitinib. Of these patients, 20% and 9% survived treatment-free, respectively.
Regan et al noted in their manuscript that “Mean TFS with grade ≥3 treatment-related adverse events (TRAEs) was a small proportion of time for both treatments.” Specifically, the mean TFS with TRAEs of 3 or greater was 0.6 months after checkpoint combination treatment versus 0.3 months after targeted therapy for patients with intermediate/poor-risk advanced RCC. It was 0.9 and 0.3 months for favorable-risk patients, respectively.
In conclusion, Regan stated, “This analysis is very patient-centered, and the implications of this work are that we have a new way to assess the value of new treatments to patients when we do clinical trials. We knew from the previous CheckMate-214 analysis that nivolumab plus ipilimumab improved survival compared with sunitinib; now, we are able to compare the way patients spent that overall survival time on these two different treatment approaches, and I think having this information is an important complement to the original trial results.”
1. Regan MM, Jegede OA, Mantia CM, et al. Treatment-free survival after immune checkpoint inhibitor therapy versus targeted therapy for advanced renal cell carcinoma: 42-month results of the CheckMate 214 trial. Published online November 10, 2021. Clin Cancer Res. doi:10.101158/1078-0432.CCR-21-2283
2. Immunotherapy may yield longer treatment-free survival than targeted therapy in advanced renal cell carcinoma. American Association for Cancer Research. November 10, 2021. Accessed November 19, 2021. https://www.aacr.org/about-the-aacr/newsroom/news-releases/immunotherapy-may-yield-longer-treatment-free-survival-than-targeted-therapy-in-advanced-renal-cell-carcinoma-patients/