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Evaluating sex as a predictive marker for response to bevacizuamb in metastatic colorectal carcinoma: Pooled analysis of 3,369 patients in the ARCAD database
Background
Previous studies suggest a possible sex-specific response to bevacizumab in metastatic colorectal carcinoma, showing a benefit in males, while the effect in females is less significant. Therefore, we evaluated response to bevacizumab according to sex.
Methods
Data from 3369 metastatic colorectal carcinoma patients enrolled on four first-line randomized trials testing chemotherapy with or without bevacizumab (2000-2007) were pooled. Association between sex and progression-free survival and overall survival was evaluated by stratified Cox regression model, adjusted for potential confounders. Predictive value was evaluated by interaction effect between sex and treatment. In a pre-planned secondary analysis, analyses were stratified using an age cut-point of 60 years to evaluate the possible role of menopausal-related effects.
Results
Median overall survival was not statistically different between males and females in the entire study population (18.8 vs. 17.6 months, respectively; adjusted hazard ratio=0.92, 95% CI=0.84-1.02, p=0.11). Bevacizumab was associated with an improved median overall survival in males and females, with a 2.3- and 0.6-months benefit, respectively, as well as an improved progression-free survival (2.0 and 1.9-months benefit, respectively). Stratified by age, bevacizumab resulted in improved progression-free survival and overall survival in males at both age categories. In females at or above the age of 60 (n=731), bevacizumab resulted in improved progression-free survival and overall survival. However, in females below the age of 60 (n=634), overall survival benefit did not reach statistical significance (adjusted hazard ratio=0.94, 95% CI 0.74-1.20).
Conclusions
Our results confirmed the median overall survival benefit from addition of bevacizumab to first-line chemotherapy in metastatic colorectal carcinoma in both sexes. Among females, the benefit was less than 1 month. For females under the age of 60, there was no overall survival benefit.
Legal entity responsible for the study
The authors.
Funding
Supported by La Fondation A.R.C.A.D., Aide et Recherche en Cancérologie Digestive.
Disclosures
R. Cohen: Honoraria (self): MSD Oncology, BMS, AMGEN; Advisory / Consultancy: BMS, MSD Oncology, Exeliome Biosciences; Research grant / Funding (self): Servier Institute; Travel / Accommodation / Expenses: MSD Oncology, MYLAN. T. Yoshino: Honoraria (self): Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Merck Biopharma, Bayer Yakuhin, Ono Pharmaceutical and MSD; Research grant / Funding (institution): Ono Pharmaceutical, Sanofi, Daiichi Sankyo, PAREXEL International, Pfizer Japan, Taiho Pharmaceutical, MSD, Amgen, Genomedia, Sysmex, Chugai Pharmaceutical and Nippon Boehringer Ingelheim. H. Lenz: Honoraria (self): BMS, Bayer, Roche; Advisory / Consultancy: Bayer, Merck, Roche; Travel / Accommodation / Expenses: BMS, Bayer, Merck KG; Shareholder / Stockholder / Stock options: Fulgent. All other authors have declared no conflicts of interest.
