As part of a partitioned survival analysis, treatment-free survival (TFS) can characterize the overall survival time patients spend between the cessation of immunotherapy and the start of subsequent therapy; both with and without toxicity. Significant TFS was reported for the nivolumab/ipilimumab arms of the CheckMate 067 and 214 trials for patients with advanced melanoma or renal cell carcinoma (aRCC), respectively, where immunotherapy was often halted for toxicity rather than a predefined treatment endpoint. We therefore sought to assess TFS in the HCRN GU16-260 trial, which was designed to reduce toxicity and cap immunotherapy duration.
Data were analyzed from 128 patients with clear-cell aRCC treated with first-line nivolumab monotherapy for up to 2 years. Salvage nivolumab/ipilimumab for up to 1 year was provided to eligible patients with disease progression at any point or stable disease at 48 weeks (29% of patients). TFS was defined as the area between Kaplan-Meier curves for a time from registration to protocol therapy cessation and for a time from registration to subsequent systemic therapy initiation or death, estimated from 36-month mean times. The time on or off protocol treatment with grade 3+treatment-related adverse events (TRAEs) was also captured.
At 36 months from enrollment, 68.3% of patients were alive: 96.8% of International Metastatic RCC Database Consortium (IMDC) favorable-risk patients and 56.6% of those with intermediate/poor-risk, respectively. The 36-month mean time on protocol therapy was 11.5 months including 0.6 months with grade 3+TRAEs (16.0 months for favorable-risk patients and 9.6 months for intermediated/poor-risk patients). The 36-month mean TFS for the whole population was 9.4 months (12.9 months including 1.5 months with grade 3+TRAEs for favorable-risk and 8.0 months including 1.0 months with grade 3+TRAEs for intermediate/poor-risk). At 36 months, 65.6% of favorable-risk patients and 27.1% of intermediate/poor-risk patients were alive and subsequent systemic treatment-free.
Nivolumab monotherapy with salvage nivolumab/ipilimumab in non-responders is an active treatment approach in treatment-naïve patients with aRCC and, similar to nivolumab/ipilimumab in CheckMate 214, results in substantial TFS and toxicity-free TFS. TFS was greatest in patients with favorable-risk disease, supporting the use of an immunotherapy-only regimen in this population.
Journal for immunotherapy of cancer. 2024 Apr 11*** epublish ***
Michael B Atkins, Opeyemi A Jegede, Naomi B Haas, David F Mcdermott, Mehmet A Bilen, Mark Stein, Jeffrey Sosman, Robert Alter, Elizabeth R Plimack, Moshe C Ornstein, Michael Hurwitz, David J Peace, David Einstein, Paul J Catalano, Hans Hammers, Meredith M Regan
Oncology, Georgetown University Medical Center, Washington, District of Columbia, USA ., Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Medicine, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA., Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Department of Hematology and Medical Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia, USA., Columbia University, New York, New York, USA., Northwestern University Department of Medicine, Chicago, Illinois, USA., John Theurer Cancer Center, Hackensack, New Jersey, USA., Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA., Taussig Cancer Institute, Cleveland, Ohio, USA., Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA., Medicine, University of Illinois at Chicago, Chicago, Illinois, USA., The University of Texas Southwestern Medical Center, Dallas, Texas, USA.