Treatment-free interval (TFI) following discontinuation of first-line nivolumab plus ipilimumab (N+I) or sunitinib (S) in patients (Pts) with advanced renal cell carcinoma (aRCC): CheckMate 214 analysis

Background: Pts with metastatic melanoma who discontinue N+I may experience sustained clinical benefit and a delayed need for subsequent therapy. In this analysis, TFI was retrospectively analyzed using data from the phase 3 CheckMate 214 trial, in which N+I demonstrated superior efficacy vs S in pts with IMDC intermediate/poor (int/poor)-risk aRCC. Methods: In CheckMate 214, pts with previously untreated clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg every 3 weeks for 4 doses followed by N 3 mg/kg every 2 weeks, or S 50 mg daily orally for 4 weeks (6-week cycles). TFI was defined as the time from last dose of N+I or S to the start of subsequent systemic therapy or death. All randomized pts with IMDC int/poor-risk aRCC (N+I, 425; S, 422) were analyzed. Kaplan–Meier curves and log-rank tests were used to compare TFI between N+I and S. Results: With median overall survival follow-up of 25.2 months, pts in the N+I arm had significantly longer time from randomization to subsequent systemic therapy or death than pts in the S arm (median, 15.4 vs 8.5 months; P < 0.0001); 2 years after randomization, 42% vs 19% of pts were alive and not requiring subsequent therapy. Overall, 320 (75%) N+I pts and 359 (85%) S pts discontinued treatment, most commonly due to disease progression (N+I, 42%; S, 58%) or study drug–related adverse events (N+I, 23%; S, 11%). In pts who discontinued, TFI was significantly longer with N+I than with S (P < 0.0001); 18 months after discontinuation, 19% of N+I pts vs 4% of S pts remained treatment-free. TFI was also significantly longer with N+I than with S, irrespective of best overall response on study (P < 0.0001). 18 months after discontinuation, 48% of N+I pts vs 6% of S pts with complete/partial response were still free of subsequent treatment; at the same time point, 13% of N+I pts vs 4% of S pts with stable disease remained treatment-free. Conclusions: The use of N+I was associated with a significant longer TFI beyond treatment discontinuation in pts with IMDC int/poor-risk aRCC and irrespective of whether pts achieved response or disease control. TFI should be considered along with traditional efficacy measures when evaluating treatment options for aRCC. Clinical trial identification: NCT02231749. Editorial acknowledgement: Professional medical writing and editorial assistance were provided by Richard Daniel, PhD, and Lawrence Hargett of PPSI (a PAREXEL company), funded by Bristol-Myers Squibb. Legal entity responsible for the study: Bristol-Myers Squibb. Funding: Bristol-Myers Squibb and ONO Pharmaceutical Company Limited. Disclosure: D.F. McDermott: Consulting or advisory role: Array BioPharma, Bristol- Myers Squibb, Eisai, Exelixis, Genentech, Merck, Novartis, Pfizer; Research funding: Prometheus (Inst). B.I. Rini: Consulting or advisory role: Bristol-Myers Squibb. R.J. Motzer: Consulting or advisory role: Eisai, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer; Research funding: Bristol-Myers Squibb, Eisai, Exelixis, Novartis, Pfizer. N.M. Tannir: Research funding: Bristol-Myers Squibb, Epizyme, Exelixis, Mirati, Novartis; Consulting or advisory role: Argos, Bristol-Myers Squibb, Eisai, Exelixis, Nektar, Novartis, Oncorena, Pfizer; Advisory board member: Eisai, Exelixis, Nektar, Novartis, Oncorena. B. Escudier: Honoraria: Bristol-Myers Squibb, Bayer, Novartis, Pfizer, Exelixis, Roche. C.K. Kollmannsberger: Honoraria: Bristol-Myers Squibb, Pfizer; Consulting or advisory role: Bristol-Myers Squibb, Pfizer. H.J. Hammers: Consulting or advisory role: Bristol-Myers Squibb, Pfizer, Exelixis; Research funding: Bristol-Myers Squibb; Travel, accommodations, expenses: Bristol Myers Squibb, Pfizer, Exelixis. C. Porta: Consulting or advisory role: Bristol-Myers Squibb, Pfizer, Novartis, Ipsen, Eisai, EUSA, Janssen. S. George: Consulting or advisory role: Bristol-Myers Squibb, Novartis, Bayer, Pfizer, Exelixis, AstraZeneca, Janssen Oncology, Corvus Pharmaceuticals, Genentech/Roche; Research funding to institution: Pfizer, Acceleron Pharma, Merck, Agensys, Novartis, Bristol-Myers Squibb, Bayer. F. Donskov: Research funding to institution: Ipsen, Novartis, Pfizer. H.P. Gurney: Consulting or Advisory Role: Astellas, Bristol-Myers Squibb, Novartis, Pfizer. M-O. Grimm: Honoraria: Pfizer, MSD, Apogepha; Consulting or advisory role: Roche; Research funding: Novartis, Bristol-Myers Squibb. T.E. Hutson: Speaker, research support and advisor: Bristol-Myers Squibb, Pfizer, Novartis, Aveo, Exelexis, Janssen. J. Doan, S. Yang, S. Rao, S. Mekan: Employment, Stock or other ownership: Bristol-Myers Squibb. A. Ambavane: Employment: Evidera, Inc. which received fees for consulting support from Bristol-Myers Squibb and EMD Serono. T. Powles: Research funding: AstraZeneca, Novartis, Roche Honoraria: AstraZeneca, Merck, Bristol-Myers Squibb, Pfizer, Roche. All other authors have declared no conflicts of interest.