A Pooled Analysis of Treatment-Free Survival in Advanced Renal Cell Carcinoma

Abstract Purpose: A clinically meaningful attribute of some immune-oncology (IO) regimens is potential durable clinical benefit during a treatment-free interval. We characterize treatment-free survival (TFS) with and without ongoing toxicity in trials of frontline IO-VEGF tyrosine kinase inhibitor (TKI) combinations in patients with advanced renal cell carcinoma (aRCC). Patients and Methods: Individual patient data were pooled by treatment arm from randomized trials submitted to the FDA evaluating IO-TKI combination in treatment-naïve aRCC with at least 30 months of median follow-up. OS, TFS, TFS with and without toxicity, and time to all protocol therapy cessation were assessed. TFS was estimated by 30-month restricted mean times defined as area between Kaplan-Meier curves for two time-to-event endpoints originating at randomization: time to all protocol therapy cessation and time to subsequent systemic therapy initiation or death. Results: Three trials met criteria for analysis; 1183 pts received IO-TKI versus 1184 on control arms received TKI alone (sunitinib [SUN]). IO-TKI and SUN groups spent 9% (2.7 months [95% confidence interval (CI): 1.8, 3.5]) and 10% (2.9 months [95% CI: 2.1, 3.8]) of the 30-mo period alive and treatment-free, respectively. Mean TFS without grade ≥3 toxicity was 1.7 and 2.3 months in IO-TKI and SUN groups, respectively. Conclusions and Relevance: In this post hoc partitioned survival analysis, TFS and TFS without toxicity appeared similar in the IO-TKI group compared to the SUN group. These findings may reflect continuation of TKI until progression per protocol design in all trials and discontinuation of IO after 2 years in 2 trials.