Treatment-Free Survival and Partitioned Survival Analysis of Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab plus Ipilimumab Versus Sunitinib: 5-Year Update of CheckMate 214

As the median overall survival of patients with advanced renal cell carcinoma has improved with novel treatment combinations, it is important to understand how patients are spending their survival time.^1-4 Treatment with immunotherapy can result in both durable disease response as well as treatment-related side effects that persist even after treatment has stopped. A partitioned survival analysis including treatment-free survival (TFS) with and without toxicity can help illustrate how patients spend their time in survival.

Checkmate 214 is a phase III clinical trial of first-line treatment with nivolumab plus ipilimumab versus sunitinib in 1096 patients with advanced renal cell carcinoma.4 With the previously reported extended follow-up of 5 years, median overall survival continues to be improved with nivolumab plus ipilimumab versus sunitinib (55.7 months vs 38.4 months) in the intent-to-treat population.5 We now report a partitioned survival analysis of time spent on therapy with and without toxicity, time spent in TFS with and without toxicity, and time spent after starting subsequent therapy.6

In the intent-to-treat population treated with nivolumab plus ipilimumab at 60 months, 8% of patients remained on nivolumab monotherapy 18% were surviving treatment-free, and for patients treated with sunitinib, 2% remained on protocol therapy and 5% were surviving treatment-free. The average time on protocol therapy with grade 2+ and grade 3+ treatment-related adverse events was greater for patients treated with sunitinib compared to nivolumab plus ipilimumab for both IMDC favorable and intermediate/poor risk groups.

TFS was longer after treatment with nivolumab plus ipilimumab versus sunitinib across all baseline variables analyzed (IMDC risk, prior nephrectomy, PD-L1, neutrophil-to-lymphocyte ratio, sarcomatoid differentiation, and presence of bone/liver metastases). In the favorable-risk population, patients treated with nivolumab plus ipilimumab spent more of their survival time treatment-free without toxicity in comparison to favorable-risk patients treated with sunitinib who spent more of the 60-month survival time on treatment with grade 2+ TRAEs. In the intermediate/poor risk population, patients spent longer time on protocol therapy without grade 2+ TRAEs, longer time in TFS without grade 2+ TRAEs, and had longer overall survival after treatment with nivolumab plus ipilimumab compared with sunitinib.

A partitioned survival analysis including TFS with and without toxicity provides a more comprehensive evaluation of the benefits and risks of treatment regimens beyond the standard outcome measures. It should be incorporated into clinical trials for a patient-centered approach. Understanding how patients spend their survival time can help in choosing a first-line treatment regimen for patients with advanced renal cell carcinoma.

Written by:

Charlene Mantia, MD, Lank Center for Genitourinary Oncology, Center for Cancer Therapeutic Innovation, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Meredith M. Regan, ScD, FASCO, Division of Biostatistics, Dana-Farber Cancer Institute, Professor of Medicine, Harvard Medical School, Boston, MA

References:

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