Efficacy and safety of cobimetinib (C) combined with vemurafenib (V) in patients (pts) with BRAFV600 mutation–positive metastatic melanoma: analysis from the 4-year extended follow-up of the phase 3 coBRIM study.

Authors

null

Brigitte Dreno

Dermatology Departement, CHU Nantes, Nantes, France

Brigitte Dreno , Paolo Antonio Ascierto , Grant A. McArthur , Victoria Atkinson , Gabriella Liszkay , Anna Maria Di Giacomo , Mario Mandalà , Lev V. Demidov , Daniil Stroyakovskiy , Luc Thomas , Luis De la Cruz-Merino , Caroline Dutriaux , Claus Garbe , Isabelle Anne Rooney , Jessie J. Hsu , Erica Park , Antoni Ribas , James M. G. Larkin

Organizations

Dermatology Departement, CHU Nantes, Nantes, France, National Tumour Institute Fondazione G. Pascale, Naples, Italy, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia, University of Queensland, Brisbane, Australia, National Institute of Oncology, Budapest, Hungary, Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia, Moscow City Oncology Hospital #62, Moscow, Russian Federation, Lyon University, Cancerology Institute of Lyon Civic Hospital, Cancer Research Centre of Lyon, Lyon, France, Pierre Benite, France, Hospital Universitario Virgen Macarena, Sevilla, Spain, Dermatology and Pediatric dermatology department, Bordeaux hospital, Bordeaux, France, Bordeaux, France, Eberhard Karls University, Tübingen, Germany, Genentech, Inc., San Francisco, CA, Genentech, Inc., South San Francisco, CA, Genentech, South San Francisco, CA, University of California, Los Angeles and the Jonsson Comprehensive Cancer Center, Los Angeles, CA, The Royal Marsden Hospital, London, United Kingdom

Research Funding

Pharmaceutical/Biotech Company

Background: The coBRIM study demonstrated that first-line C+V improved progression-free (PFS) and overall survival (OS) compared with placebo (P)+V in pts with BRAFV600-mutated advanced melanoma. We report updated survival outcomes and safety after extended follow-up. Methods: coBRIM was a double-blind, multicenter study in which 495 patients were randomized to receive C (60 mg once daily for 21 days followed by a 7-day rest period in each 28-day cycle; n = 247) or P (n = 248) in combination with V (960 mg twice daily). PFS and OS were primary and secondary endpoints, respectively. Results: At database closure, median follow-up duration for the overall intent-to-treat population was 18.6 months (range, 0.5–55.1 months); 176 pts (71%) in the C+V arm and 190 pts (77%) in the P+V arm had discontinued the study, with the most common reason being death (C+V = 148 pts [60%]; P+V = 162 pts [65%]). Median PFS among pts receiving C+V was 12.6 months (95% confidence interval [CI], 9.5–14.7 months) vs 7.2 months (95% CI, 5.6–7.5 months) in pts receiving P+V. Median OS among pts receiving C+V was 22.5 months (95% CI, 20.3–28.8 months) vs 17.4 months (95% CI, 15.2–20.5 months) in pts receiving P+V. A greater proportion of pts receiving C+V were alive at 1, 2, 3 and 4 years vs pts receiving P+V (Table). Median duration of treatment in the C+V arm was 9.0 months (range, 0.1–53.1 months) for C and 9.2 months (range, 0.3–53.3 months) for V. Pts in the P+V arm had a shorter median duration of treatment of 5.6 months (range, 0.2–43.9 months) for P and 5.7 months (0.2–53.2 months) for V. Grade 3/4 adverse events (AEs) were reported in 75% and 61% of pts in the C+V and P+V arms, respectively. Grade 5 AEs were reported in 2% of pts in each study arm. A larger proportion of pts discontinued C+V (19%) versus P+V (10%) due to AEs. Conclusions: Extended follow-up of the phase 3 coBRIM study confirmed the survival benefit of C+V over P+V. No new safety signals were observed. Clinical trial information: NCT01689519

Landmark OS, % (95% CI)
C+VP+V
1-year74.5 (68.9–80.1)63.8 (57.6–70.0)
2-year49.0 (42.5–55.6)39.0 (32.7–45.4)
3-year38.5 (32.1–44.9)31.1 (25.0–37.2)
4-year34.7 (28.4–41.0)29.2 (23.1–35.2)

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Abstract Details

Meeting

2018 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Melanoma/Skin Cancers

Track

Melanoma/Skin Cancers

Sub Track

Advanced/Metastatic Disease

Clinical Trial Registration Number

NCT01689519

Citation

J Clin Oncol 36, 2018 (suppl; abstr 9522)

DOI

10.1200/JCO.2018.36.15_suppl.9522

Abstract #

9522

Poster Bd #

349

Abstract Disclosures