Jiaxi Zhou

List of Trials Included in Analysis and Key Design Features

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).Experimental Design: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; 1,183 patients received IO-TKI versus 1,184 on control arms receiving 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-month 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:In this post hoc partitioned survival analysis, TFS and TFS without toxicity appeared similar in the IO-TKI group compared with the SUN group. These findings may reflect contin-uation of TKI until progression per protocol design in all trials and discontinuation of IO after 2 years in two trials.See related commentary by Stadler and Karrison, p. 3098

Treatment-Free Survival and Time on Protocol Therapy With and Without Toxicity in IO-VEGF TKI and Sunitinib Groups

Time on Each Drug as Monotherapy in IO-TKI Combination

Time on Each Drug as Monotherapy in IO-TKI Combination

Time on Each Drug as Monotherapy in IO-TKI Combination

Treatment-Free Survival and Time on Protocol Therapy With and Without Toxicity in IO-VEGF TKI and Sunitinib Groups

Treatment-Free Survival and Time on Protocol Therapy With and Without Toxicity in IO-VEGF TKI and Sunitinib Groups

Treatment-Free Survival in Advanced Renal Cell Carcinoma Trials Evaluating Immuno-Oncology-VEGF TKI Combinations: Sunitinib Group

List of Trials Included in Analysis and Key Design Features