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.
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.
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.
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
Legal entity responsible for the study
Bristol-Myers Squibb and ONO Pharmaceutical Company Limited.
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.
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.