Treatment-free survival outcomes from the phase II study of nivolumab and salvage nivolumab/ipilimumab in advanced clear cell renal cell carcinoma (HCRN GU16-260-Cohort A).

Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Competing Interests: Competing interests: MBA has/had an advisory role for Bristol-Myers Squibb, Merck, Novartis, Eisai, Exelixis, Aveo, Pfizer, Werewolf, Fathom, Pyxis Oncology, PACT, Elpis, X4Pharma, ValoHealth, ScholarRock, Surface, Takeda, Simcha, Roche, SAB Bio, Pliant Therapeutics, Atreca, OncoRena, Sanofi and GSK and has served as a consultant: Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche, Agenus, Asher Bio, and AstraZeneca. He reports research support to his institution from Bristol-Myers Squibb and Merck. He holds stock/stock options in Pyxis Oncology, Werewolf and Elpis. OAJ—none. NBH is a paid consultant to BMS, Eisai, Exelixis, Merck and Roche Genentech. DFM has acted as a paid consultant for and/or as a member of the advisory boards of BMS, Pfizer, Merck, Alkermes, Inc, EMD Serono, Eli Lilly and Company, Iovance, Eisai Inc., Werewolf Technologies, Calithera Biosciences, Synthekine, Inc., Johnson served on speakers bureaus for Bristol Myers Squibb and Merck; received institutional research funding from Bristol Myers Squibb, Pfizer, Merck, AstraZeneca, Astellas, Aravive, and Surface Oncology; has received reimbursement for travel and accommodations expenses from Bristol Myers Squibb, Pfizer, Eisai, and Exelixis. MH has served on Advisory Boards for Bristol Myers Squibb, CRISPR Therapeutics, Exelixis, Nektar Therapeutics, Janssen and has received research support to his institution from Alpine, Achilles Therapeutics, Apexigen, Arrowhead, Astellas, AstraZeneca, Bayer, Bristol Myer Squibb, CRISPR Therapeutics, Corvus, Eli Lilly, Endocyte, Fate Therapeutics, Genentech, Genmab, GSK, Innocrin, Iovance, KSQ, Merck, Nektar Therapeutics, Novartis, Pfizer, Progenics, Sanofi Aventis, SeaGen, Tmunity, Torque, Unum. He also reports Spouse salary from Gamida Cell, Arvinas. DJP holds stock in Bristol-Myers Squibb and Merck. DE reports research funding to institution from Bristol-Myers Squibb, Cardiff Oncology, Mink Therapeutics, Novartis, Puma Biotechnology, and Sanofi, as well as discounted research sequencing from Foundation Medicine and honorarium from OncLive. PJC—none. HH has acted as a paid consultant for and/or as a member of the advisory boards of Exelixis, BMS, Pfizer, Merck, Corvus, Armo Biosciences, Eisai, Eli Lilly, Surface Oncology, Aveo and Novartis and has received grants to his institution from Merck, Bristol-Myers Squibb, Surface Oncology and Aravive for work performed as outside of the current study. MMR reports research funding to institution from AstraZeneca, Bayer, Biotheranostics, Bristol-Myers Squibb, DebioPharm, Ipsen, Novartis, Pfizer, Roche, TerSera Therapeutics, all outside of the current study, and a consulting or advisory role for AstraZeneca, Bristol-Myers Squibb, DebioPharm, Ipsen, TerSera Therapeutics, Tolmar Pharmaceuticals.
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