Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study.

Autor:	Dréno B; Department of Dermato Cancerology, Nantes University, Nantes, France., Ribas A; Department of Medicine, Hematology/Oncology, Jonsson Comprehensive Cancer Center, The University of California, Los Angeles, Los Angeles, USA., Larkin J; Department of Medicine, Royal Marsden NHS Foundation Trust, London, UK., Ascierto PA; Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy., Hauschild A; Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany., Thomas L; Department of Dermatology, Centre Hospitalier Lyon Sud, Lyon 1 University, Lyons Cancer Research Center, France., Grob JJ; Dermatology and Cutaneous Oncology, Aix-Marseille University Hôpital de la Timone AP-HM, Marseille, France., Koralek DO; Department of Clinical Development, Genentech Inc., South San Francisco, USA., Rooney I; Product Development Oncology, Genentech Inc., South San Francisco, USA., Hsu JJ; Biostatistics, Genentech Inc., South San Francisco, USA., McKenna EF; Medical Affairs, Genentech, Inc., South San Francisco, USA., McArthur GA; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2017 May 01; Vol. 28 (5), pp. 1137-1144.
DOI:	10.1093/annonc/mdx040
Abstrakt:	Background: In the coBRIM phase III trial, the addition of cobimetinib, an MEK inhibitor, to vemurafenib, a BRAF inhibitor, significantly improved progression-free survival [hazard ratio (HR), 0.58; P < 0.0001] and overall survival (HR, 0.70; P = 0.005) in advanced BRAF-mutated melanoma. Here, we report on the incidence, course, and management of key adverse events (AEs) in the coBRIM study. Patients and Methods: Patients were randomly assigned 1:1 to receive vemurafenib (960 mg twice a day) and either cobimetinib (60 mg once a day, 21 days on/7 days off) or placebo. In addition to standard safety evaluations, patients underwent regular ophthalmic, cardiac, and dermatologic surveillance examinations. Results: Of 495 patients recruited to the study, 493 patients received treatment and constituted the safety population (cobimetinib combined with vemurafenib, 247; vemurafenib, 246). At data cut-off (30 September 2015), median follow-up was 18.5 months. Nearly every patient experienced an AE. In patients who received cobimetinib combined with vemurafenib, the frequency of grade ≥3 AEs was higher than in patients who received vemurafenib alone (75% versus 61%). Most AEs, including grade ≥3 AEs, occurred within the first treatment cycle. After the first cycle (28 days), the incidence of common AEs (rash, diarrhoea, photosensitivity, elevated creatine phosphokinase, serous retinopathy, pyrexia, and liver laboratory abnormalities) decreased substantially over time. Most AEs were managed conservatively by supportive care measures, dose modifications of study treatment, and, occasionally, permanent treatment discontinuation. Conclusions: These data indicate that most AEs arising from treatment with cobimetinib combined with vemurafenib generally occur early in the treatment course, are mild or moderate and are manageable by patient monitoring, dose modification and supportive care. Clinicaltrials.gov: NCT01689519. (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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