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Characterization of response to nivolumab plus ipilimumab (N+I) or sunitinib (S) in patients (Pts) with previously untreated advanced renal cell carcinoma (arcc): Checkmate 214

2018; Elsevier BV; Volume: 29; Linguagem: Inglês

10.1093/annonc/mdy283.084

1569-8041

Brian I. Rini, Nizar M. Tannir, Bernard Escudier, David F. McDermott, Marc‐Oliver Grimm, Camillo Porta, T. Powles, Christian Kollmannsberger, Howard Gurney, Scott S. Tykodi, Michael R. Harrison, D.Y.C. Heng, Viktor Grünwald, Toni K. Choueiri, Sabeen Mekan, M. Brent McHenry, Hans J. Hammers, Robert J. Motzer, Saby George,

Cancer Immunotherapy and Biomarkers

Background: N+I demonstrated superior objective response rate (ORR) and overall survival (OS) vs sunitinib in pts with IMDC intermediate/poor (int/poor)-risk aRCC in the phase 3 CheckMate 214 trial. Further characterization of response may inform clinical practice. Methods: In CheckMate 214, pts with previously untreated aRCC were randomly assigned 1:1 to N 3 mg/kg + I 1 mg/kg Q3W for 4 doses then N 3 mg/kg Q2W or S 50 mg QD for 4 weeks on, 2 weeks off. Efficacy, safety, and quality of life (QoL) were explored in int/poor-risk pts with complete response (CR) or partial response to N+I or S. Results: At 25.2 months median follow-up, confirmed ORR per independent radiology review committee in int/poor-risk pts was 42% for N+I vs 27% for S (P < 0.001; Table) with 36% vs 18% of pts achieving best tumor reduction ≥50% with N+I vs S. Of N+I vs S responders, 72% vs 63% have ongoing response, 47% and 34% remain on treatment, and 53% and 66% discontinued, most often for disease progression (N+I, 22%; S, 40%) or toxicity (N+I, 23%; S, 13%). N+I responders received a median of 21.0 months of treatment (vs 3.8 months for N+I nonresponders). Response lasting ≥18 months was seen in 13% of N+I and 4% of S pts. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 52% of N+I and 68% of S responders. Mean change from baseline at 24 weeks in Functional Assessment of Cancer Therapy–Kidney Symptom Index 19 score was 3.0 in N+I responders (better) vs − 0.7 in S responders (worse). Updated 3-year data on responders, including use of subsequent therapies, will be presented. Conclusions: ORR and OS were significantly improved with N+I compared with S in pts with int/poor-risk aRCC in CheckMate 214. Responses to N+I were more likely to be CRs and were more durable than responses to S. High-grade TRAEs were less frequent and QoL was better in N+I responders compared with S responders.Table: 875POutcomeN+I int/poor-risk ptsS int/poor-risk ptsTotal n = 425CR n = 40PR n = 137Total n = 422CR n = 5PR n = 107BOR (95% CI), %42 (37–47)93227 (22–31)125Median (range) time to response, months2.8 (0.9–11.3)2.8 (0.9–11.0)2.8 (1.4–11.3)3.0 (0.6–15.0)2.9 (2.8–4.2)3.1 (0.6–15.0)Median (95% CI) duration of response, monthsNR (21.8–NE)NRNR (18.8–NE)18.2 (14.8–NE)NR18.2 (13.9–NE)Pts with ongoing response in responders, n/N (%)128/177 (72)34/40 (85)94/137 (69)71/112 (63)5/5 (100)66/107 (62)12-month PFS rate (95% CI), %50 (44–55)97 (83–100)81 (73–86)43 (37–48)100 (100–100)79 (69–86)18-month OS rate (95% CI), %78 (74–81)100 (100–100)94 (89–97)68 (63–72)100 (100–100)92 (85–96)BOR, best overall response; NE, not estimable; NR, not reached; PR, partial response Open table in a new tab BOR, best overall response; NE, not estimable; NR, not reached; PR, partial response Clinical trial identification: NCT02231749. Editorial acknowledgement: Professional medical writing assistance was provided by Nicolette Belletier, PhD, of PPSI, funded by Bristol-Myers Squibb. Legal entity responsible for the study: Bristol-Myers Squibb. Funding: Bristol-Myers Squibb and Ono Pharmaceutical Company Limited. Disclosure: B.I. Rini: Consulting or Advisory role: Bristol-Myers Squibb. 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. D.F. McDermott: Consulting or Advisory role: Array BioPharma, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Merck, Novartis, Pfizer; Research funding: Prometheus (Inst). M-O. Grimm: Honoraria: Pfizer, MSD, Apogepha; Consulting or Advisory role: Roche; Research funding: Novartis, Bristol-Myers Squibb. C. Porta: Consulting or Advisory role: Bristol-Myers Squibb, Pfizer, Novartis, Ipsen, Eisai, EUSA, Janssen. T. Powles: Research funding: AstraZeneca, Novartis, Roche; Honoraria: AstraZeneca, Merck, Bristol-Myers Squibb, Pfizer, Roche. C.K. Kollmannsberger: Honoraria: Bristol-Myers Squibb, Pfizer; Consulting or Advisory role: Bristol-Myers Squibb, Pfizer. H.P. Gurney: Consulting or Advisory role: Astellas, Bristol-Myers Squibb, Novartis, Pfizer. S.S. Tykodi: Consulting or Advisory role: Bristol-Myers Squibb, Calithera Biosciences, Prometheus Laboratories; Research funding to institution: Bristol-Myers Squibb, Calithera Biosciences, Merck, Nektar Therapeutics, Peloton Therapeutics, Jounce Therapeutics, Pfizer, Genentech, Prometheus Laboratories, Argos Therapeutics. D.Y.C. Heng: Consulting or Advisory role: Bristol-Myers Squibb, Pfizer, Novartis. V. Grünwald: Honoraria: Bristol-Myers Squibb; Consulting or Advisory role: Bristol-Myers Squibb, Novartis, Pfizer, Bayer; Speakers' Bureaus: Bristol-Myers Squibb, Novartis, Pfizer. T.K. Choueiri: Consulting or Advisory role: Merck, Novartis, Peloton, Pfizer, Roche, Eisai, Tracon, Bayer, Cerulean, Foundation Medicine, Inc., GlaxoSmithKline, Prometheus, Corvus; Research Funding to institution: Merck, Novartis, Peloton, Pfizer, Roche, Eisai, Tracon. S. Mekan: Employment or Other ownership: Bristol-Myers Squibb. 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. R.J. Motzer: Consulting or Advisory role: Eisai, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer; Research funding: Bristol-Myers Squibb, Eisai, Exelixis, Novartis, Pfizer. S. George: Consulting or Advisory role: Bristol-Myers Squibb, Novartis, Bayer, Pfizer, Exelixis, AstraZeneca, Janssen Oncology, Corvus Pharmaceuticals, Genentech/Roche; Research funding (inst): Pfizer, Acceleron Pharma, Merck, Agensys, Novartis, Bristol-Myers Squibb, Bayer. All other authors have declared no conflicts of interest.