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.
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.
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.Table: 875P
|Outcome||N+I int/poor-risk pts||S int/poor-risk pts|
|Total n = 425||CR n = 40||PR n = 137||Total n = 422||CR n = 5||PR n = 107|
|BOR (95% CI), %||42 (37–47)||9||32||27 (22–31)||1||25|
|Median (range) time to response, months||2.8 (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, months||NR (21.8–NE)||NR||NR (18.8–NE)||18.2 (14.8–NE)||NR||18.2 (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
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.
Clinical trial identification
Legal entity responsible for the study
Bristol-Myers Squibb and Ono Pharmaceutical Company Limited.
Professional medical writing assistance was provided by Nicolette Belletier, PhD, of PPSI, funded by Bristol-Myers Squibb.
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.