Characterization of Response to Nivolumab Plus Ipilimumab (N+I) or Sunitinib (S) in Patients (Pts) With Previously Untreated Advanced Renal Cell Ca...

Date 22 October 2018
Event ESMO 2018 Congress
Session Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care
Topics Renal Cell Cancer
Presenter Brian Rini
Citation Annals of Oncology (2018) 29 (suppl_8): viii303-viii331. 10.1093/annonc/mdy283
Authors B.I. Rini1, N.M. Tannir2, B. Escudier3, D.F. McDermott4, M. Grimm5, C. Porta6, T. Powles7, C.K. Kollmannsberger8, H.P. Gurney9, S.S. Tykodi10, M. Harrison11, D.Y.C. Heng12, V. Grünwald13, T.K. Choueiri14, S. Mekan15, M..B. McHenry15, H.J. Hammers16, R.J. Motzer17, S. George18
  • 1Department Of Hematology And Oncology, Cleveland Clinic Taussig Cancer Institute, 44195 - Cleveland/US
  • 2Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 77030-3721 - Houston/US
  • 3Department Of Medical Oncology, Gustave Roussy, 94805 - Villejuif/FR
  • 4Department Of Medicine, Beth Israel Deaconess Med. Center, 2215 - Boston/US
  • 5Department Of Urology, Jena University Hospital, 7740 - Jena/DE
  • 6Department Of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo University Hospital Foundation, 27100 - Pavia/IT
  • 7Department Of Medicine, Barts Cancer Institute, EC1M 6BQ - London/GB
  • 8Department Of Medicine, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 9Department Of Medical Oncology, Westmead Hospital and Macquarie University, 2145 - Westmead/AU
  • 10Department Of Medicine, Fred Hutchinson Cancer Research Center, 98109 - Seattle/US
  • 11Department Of Medicine, Duke University Medical Center, 27710 - Durham/US
  • 12Department Of Oncology, Tom Baker Cancer Center, T2N 4N2 - Calgary/CA
  • 13Department Of Hematology And Oncology, Hannover Medical School, 30625 - Hannover/DE
  • 14Department Of Genitourinary Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 15Clinical Development, Bristol-Myers Squibb Company, NJ 08648 - Lawrenceville/US
  • 16Department Of Hematology And Oncology, University of Texas Southwestern Medical Center at Dallas, 75390-8576 - Dallas/US
  • 17Department Of Genitourinary Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 18Department Of Medicine, Roswell Park Cancer Institute, 14263 - Buffalo/US

Abstract

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.Table: 875P

OutcomeN+I int/poor-risk ptsS int/poor-risk pts
Total n = 425CR n = 40PR n = 137Total n = 422CR n = 5PR n = 107
BOR (95% CI), %42 (37–47)93227 (22–31)125
Median (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

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.

Clinical trial identification

NCT02231749.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb and Ono Pharmaceutical Company Limited.

Editorial Acknowledgement

Professional medical writing assistance was provided by Nicolette Belletier, PhD, of PPSI, funded by Bristol-Myers Squibb.

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.