Treatment-Free Interval (TFI) Following Discontinuation of First-Line Nivolumab Plus Ipilimumab (N+I) or Sunitinib (S) in Patients (Pts) With Advan...

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 David McDermott
Citation Annals of Oncology (2018) 29 (suppl_8): viii303-viii331. 10.1093/annonc/mdy283
Authors D.F. McDermott1, B.I. Rini2, R.J. Motzer3, N.M. Tannir4, B. Escudier5, C.K. Kollmannsberger6, H.J. Hammers7, C. Porta8, S. George9, F. Donskov10, H.P. Gurney11, M. Grimm12, M. Harrison13, T.E. Hutson14, J. Doan15, S. Yang15, S. Rao15, S. Mekan16, A. Ambavane17, T. Powles18
  • 1Department Of Medicine, Beth Israel Deaconess Medical Center, Dana–Farber/Harvard Cancer Center, 2215 - Boston/US
  • 2Department Of Hematology And Oncology, Cleveland Clinic Taussig Cancer Institute, 44195 - Cleveland/US
  • 3Department Of Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 4Department Of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, 77030-3721 - Houston/US
  • 5Department Of Medical Oncology, Gustave Roussy, 94805 - Villejuif/FR
  • 6Division Of Medical Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 7Division Of Hematology And Oncology, UT Southwestern – Kidney Cancer Program, 75390-8576 - Dallas/US
  • 8Department Of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo University Hospital Foundation, 27100 - Pavia/IT
  • 9Department Of Medicine, Roswell Park Cancer Institute, 14263 - Buffalo/US
  • 10Department Of Oncology, Aarhus University Hospital, 8000 - Aarhus/DK
  • 11Department Of Medical Oncology, Westmead Hospital and Macquarie University, 2145 - Westmead/AU
  • 12Department Of Urology, Jena University Hospital, 7740 - Jena/DE
  • 13Department Of Medicine, Duke University Medical Center, 27710 - Durham/US
  • 14Department Of Medicine, Texas A&M HSC College of Medicine, 75246 - Dallas/US
  • 15Health Economics And Outcomes Research, Bristol-Myers Squibb, 08540 - Princeton/US
  • 16Health Economics And Outcomes Research, Bristol-Myers Squibb, NJ 08648 - Lawrenceville/US
  • 17Modeling And Simulation, Evidera Inc, W6 8DL - London/GB
  • 18Department Of Medicine, Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, Royal Free NHS Trust, EC1M 6BQ - London/GB

Abstract

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.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb and ONO Pharmaceutical Company Limited.

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.

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.