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

Ofer Margalit*, William S. Harmsen, Einat Shacham-Shmueli, Molly M. Voss, Ben Boursi, Anna D. Wagner, Romain Cohen, Curtis L. Olswold, Leonard B. Saltz, Daniel A. Goldstein, Herbert Hurwitz, Niall C. Tebbutt, Fairooz F. Kabbinavar, Richard A. Adams, Benoist Chibaudel, Axel Grothey, Takayuki Yoshino, John Zalcberg, Aimery de Gramont, Qian ShiHeinz Josef Lenz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)162-170
Number of pages9
JournalEuropean Journal of Cancer
Volume178
DOIs
StatePublished - Jan 2023

Funding

FundersFunder number
ARCAD Foundation

    Keywords

    • ARCAD
    • Age
    • Bevacizumab
    • Colorectal carcinoma
    • Metastatic
    • Sex

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