Evaluating sex as a predictive marker for response to bevacizumab in metastatic colorectal carcinoma: Pooled analysis of 3,369 patients in the ARCAD database Journal Article


Authors: Margalit, O.; Harmsen, W. S.; Shacham-Shmueli, E.; Voss, M. M.; Boursi, B.; Wagner, A. D.; Cohen, R.; Olswold, C. L.; Saltz, L. B.; Goldstein, D. A.; Hurwitz, H.; Tebbutt, N. C.; Kabbinavar, F. F.; Adams, R. A.; Chibaudel, B.; Grothey, A.; Yoshino, T.; Zalcberg, J.; de Gramont, A.; Shi, Q.; Lenz, H. J.
Article Title: Evaluating sex as a predictive marker for response to bevacizumab in metastatic colorectal carcinoma: Pooled analysis of 3,369 patients in the ARCAD database
Abstract: Background: Previous studies suggest a possible sex-specific response to bevacizumab in metastatic colorectal carcinoma (mCRC), showing a benefit in males, while the effect in females is less significant. Methods: Data from 3369 patients with mCRC enrolled on four first-line randomised trials testing chemotherapy with or without bevacizumab (2000–2007) were pooled. Association between sex and progression-free survival and overall survival (OS) 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: Bevacizumab was associated with an improved median OS in males and females, with a 2.3- and 0.6-months benefit, respectively. Stratified by age, bevacizumab resulted in improved OS in males at both age categories. In females at or above the age of 60 (n = 731), bevacizumab resulted in improved OS. However, in females below the age of 60 (n = 634), OS benefit did not reach statistical significance (adjusted hazard ratio = 0.94, 95% confidence interval 0.74–1.20). Conclusions: Our results confirmed the OS benefit from the addition of bevacizumab to first-line chemotherapy in mCRC in both sexes. Among females, the benefit was less than 1 month. For females under the age of 60, there was no survival benefit. These findings could be used to relieve financial toxicity or be redistributed within healthcare systems for other health-related purposes. © 2022 The Author(s)
Keywords: adult; cancer chemotherapy; controlled study; aged; disease-free survival; middle aged; major clinical study; overall survival; clinical trial; bevacizumab; fluorouracil; disease free survival; antineoplastic agent; progression free survival; estrogen responsive element; antineoplastic combined chemotherapy protocols; practice guideline; pathology; age; colorectal carcinoma; colorectal neoplasms; confidence interval; liver metastasis; lung metastasis; proportional hazards model; statistical significance; colorectal tumor; health care system; peritoneum metastasis; meta analysis; predictive value; metastatic; sex; secondary analysis; metastatic colorectal cancer; humans; human; male; female; article; financial distress; arcad
Journal Title: European Journal of Cancer
Volume: 178
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2023-01-01
Start Page: 162
End Page: 170
Language: English
DOI: 10.1016/j.ejca.2022.10.022
PUBMED: 36446161
PROVIDER: scopus
DOI/URL:
Notes: Article -- Erratum issued, see DOI: 10.1016/j.ejca.2023.113339 -- Export Date: 3 January 2023 -- Source: Scopus
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  1. Leonard B Saltz
    791 Saltz