Impact of depth of response on survival in patients treated with cobimetinib ± vemurafenib: pooled analysis of BRIM-2, BRIM-3, BRIM-7 and coBRIM

Autor: Grant A. McArthur, Keith T. Flaherty, Antoni Ribas, Brigitte Dréno, Axel Hauschild, Yeung-Chul Mun, Paolo A. Ascierto, Qian Zhu, James Larkin, Edward McKenna, Matthew Wongchenko, Yibing Yan, Karl D. Lewis
Rok vydání: 2019
Předmět:
Oncology
Cancer Research
Time Factors
Administration
Oral
Gene Expression
Kaplan-Meier Estimate
Placebos
chemistry.chemical_compound
Prognostic markers
Piperidines
Antineoplastic Combined Chemotherapy Protocols
Multicenter Studies as Topic
Vemurafenib
Melanoma
Cancer
Randomized Controlled Trials as Topic
Clinical Trials as Topic
Treatment efficacy
Progression-Free Survival
Tumor Burden
Pooled analysis
Treatment Outcome
Quartile
Injections
Intravenous
Administration
Public Health and Health Services
Intravenous
medicine.drug
Proto-Oncogene Proteins B-raf
Oral
medicine.medical_specialty
Oncology and Carcinogenesis
Antineoplastic Agents
Article
Injections
Internal medicine
Genetics
medicine
Humans
In patient
Oncology & Carcinogenesis
Prognostic models
Cobimetinib
Mitogen-Activated Protein Kinase Kinases
business.industry
medicine.disease
chemistry
Azetidines
business
Zdroj: British journal of cancer, vol 121, iss 7
British Journal of Cancer
Popis: Background This pooled analysis investigated the prognostic value of depth of response in two cohorts of patients with BRAFV600-mutated metastatic melanoma treated with vemurafenib or cobimetinib plus vemurafenib. Methods The data were pooled from BRIM-2, BRIM-3, BRIM-7 and coBRIM. Association of depth of response with survival was estimated by Cox proportional hazards regression, adjusted for clinically relevant covariates. Depth of response was analysed in previously identified prognostic subgroups based on disease characteristics and gene signatures. Results Greater tumour reduction and longer time to maximal response were significantly associated with longer progression-free survival (PFS) and overall survival (OS) when evaluated as continuous variables. Patients with the deepest responses had long-lasting survival outcomes (median PFS: 14 months; OS: 32 months with vemurafenib; not estimable with cobimetinib plus vemurafenib). Cobimetinib plus vemurafenib improved depth of response versus vemurafenib monotherapy regardless of other prognostic factors, including gene signatures. Conclusions Greater depth of response was associated with improved survival, supporting its utility as a measure of treatment efficacy in melanoma and further evaluation of its incorporation into existing prognostic models. Cobimetinib plus vemurafenib improved outcomes across quartiles of response regardless of prognostic factors or gene signatures and provided durable survival benefits in patients with deep responses.
Databáze: OpenAIRE
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