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).
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.
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.
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2024 Feb 28 [Epub ahead of print]
Elaine Chang, Jiaxi Zhou, Chi Song, Haley Gittleman, Laura Fernandes, Chana Weinstock, Michael B Atkins, Sundeep Agrawal, Rajeshwari Sridhara, Nicole Gormley, Shenghui Tang, Daniel L Suzman, Laleh Amiri-Kordestani, Paul G Kluetz, Richard Pazdur, Brian I Rini, David F McDermott, Meredith M Regan
United States Food and Drug Administration, Silver Spring, MD, United States., BeiGene, Fulton, MD, United States., Georgetown University Medical Center, Washington, DC, United States., Food and Drug Administration Center for Drug Evaluation and Research, Silver Spring, United States., Food and Drug Administration, Silver Spring, MD, United States., Vanderbilt University, Nashville, TN, United States., Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States., Dana-Farber Cancer Institute, Boston, MA, United States.