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Poster display session

2113 - Impact of duration of response (DOR) on overall survival (OS) in patients with metastatic melanoma treated with dacarbazine (DTIC), vemurafenib (V), or cobimetinib plus vemurafenib (C+V): a pooled analysis


10 Sep 2017


Poster display session


Cytotoxic Therapy;  Cancers in Adolescents and Young Adults (AYA);  Melanoma


Karl Lewis


Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377


K. Lewis1, J. Larkin2, A. Ribas3, K.T. Flaherty4, G.A. McArthur5, P.A. Ascierto6, B. Dréno7, E. McKenna8, Q. Zhu9, Y. Mun10, A. Hauschild11

Author affiliations

  • 1 Medicine, University of Colorado Comprehensive Cancer Center, 80045 - Aurora/US
  • 2 Oncology, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 3 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles/US
  • 4 Medicine, Massachusetts General Hospital, 02114 - Boston/US
  • 5 Department Of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne/AU
  • 6 Melanoma, Cancer Immunotherapy And Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione Pascale, 80131 - Naples/IT
  • 7 Dermatology, Nantes University, Nantes/FR
  • 8 Product Development, Genentech, Inc., South San Francisco/US
  • 9 Oncology, Genentech, Inc., South San Francisco/US
  • 10 Product Development, Genentech, Inc., 94080 - South San Francisco/US
  • 11 Dermatology, University Hospital Schleswig-Holstein, 24105 - Kiel/DE


Abstract 2113


Evaluation of treatment efficacy in oncology using OS is confounded by survival benefit from post-progression treatment. We pooled data from the BRIM-2, -3, -7, and coBRIM studies (BRAF inhibitor–naive patients with BRAFV600-mutated metastatic melanoma) to evaluate whether DOR could be a surrogate for OS.


Time-dependent Cox proportional hazards regression was used to model the association of DOR (interval from date of first RECIST response to progressive disease [PD] or death) with OS. The risk of death for DORs of 1–10 months (in 1-month increments) was evaluated. Patients with best response of stable disease or PD [nonresponders (NR)] were assigned a DOR of zero. Models were adjusted for time-fixed baseline covariates (ECOG status, demographics, disease covariates, and first-line treatment), and time-dependent covariates (DOR and post-progression treatment [immunotherapy, targeted therapy, or other]).


This analysis included 1365 patients (DTIC = 338; V = 717; C+V = 310). Objective response was 47.5% for the overall population and 11.5%, 53.6%, and 72.9% for the DTIC, V, and C+V cohorts, respectively. Median DOR was 9.3 months in the overall population and 6.4, 7.6, and 14.6 months in the DTIC, V, and C + V cohorts, respectively. Cox proportional hazards adjusted for time-dependent covariates showed a significant and progressive reduction in the risk of death with increasing DOR vs NR. The absolute risk of death decreased by a mean of ≈6.3–7.7% per month increase in DOR in the overall population and across treatment cohorts (Table). Sensitivity analyses in responders only showed similar results.Table:

1241P Hazard of death by duration in response (excluding time-dependent PD variables)

Patient cohortDOR of 1 monthDOR of 10 monthsMean per month HR decreaseRange of HR decreaseP-valuea
HR (95% CI)HR (95% CI)
All patients0.85 (0.82–0.87)0.19 (0.14–0.25)0.0730.034–0.130


These exploratory analyses suggest that DOR is independently associated with OS outcomes regardless of treatment and merits further exploration as a surrogate endpoint to assess long-term treatment benefit.

Clinical trial identification

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.


F. Hoffmann-LaRoche Ltd.


K. Lewis: Grants from Roche/Genentech, Amgen, EMD Serono, and Incyte, and personal fees from Roche/Genentech, Incyte, and SunPharma. J. Larkin: Institutional research support from MSD, Bristol-Myers Squibb, Pfizer, and Novartis and nonremunerated consultant for GSK, Novartis, MSD, Bristol-Myers Squibb, Pfizer, and Roche/Genentech. A. Ribas: Owns stock in Kite Pharma and has received honoraria from Roche, Amgen, Pfizer, and Merck. All monies paid to Dr. Ribas are deposited into the Division Account at the David Geffen School of Medicine and do not constitute personal income. K.T. Flaherty: Consultant for Roche. G.A. McArthur: Research grant support from Pfizer, Celgene, Ventana; consultant for Provectus; uncompensated consultancy for Pfizer, Millennium, GSK, Roche‐Genentech, Novartis, Bristol-Myers Squibb, and Amgen P.A. Ascierto: Consulting or advisory role for Amgen, Array, Bristol-Myers Squibb, Genentech/Roche, Merck Serono, Merck Sharp & Dohme, Novartis, and Pierre-Fabre, and research funding from Bristol-Myers Squibb, Genentech/Roche, and Array. B. Dréno: Personal fees from Roche, Bristol-Myers Squibb, Novartis, GlaxoSmithKline, and Amgen. E. McKenna: Employee, Genentech, Inc. Q. Zhu, Y. Mun: Employment, Genentech, Inc. A. Hauschild: Personal fees from Roche, Amgen, Bristol-Myers Squibb, Celgene, Eisai, GlaxoSmithKline, MedImmune, Merck Serono, Merck Sharp & Dohme/Merck, Novartis, Oncosec, and MELA Sciences.

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