Sex-based prognosis in industry-sponsored advanced solid tumour trials: an individual participant data meta-analysis of survival and adverse events

Abstract

Background: Sex is a recognised modifier of physiology, immunity, and social exposures, yet its independent association with survival and adverse event (AE) prognosis in contemporary anticancer therapy remains poorly defined. The aim of the present study was to assess the association between patient sex and OS, PFS, and grade ≥3 AEs across a pooled individual participant data (IPD) meta-analysis.

Methods: IPD supporting FDA approval of anticancer medicines for solid tumours between 2011 and 2021 were accessed via the Vivli and YODA data sharing platforms. A two-stage random-effects meta-analysis approach was employed, using Cox proportional hazards regression to estimate sex-based prognostic differences in overall survival (OS), progression-free survival (PFS), and grade ≥3 AEs. Analyses were adjusted for key baseline covariates.

Results: In a pooled cohort of 20,806 participants from 39 phase II-III trials supporting US FDA approvals of anticancer medicines for advanced solid tumours, across 12 tumour types, female sex was associated with significantly improved OS (HR 0.79, 95% CI 0.73-0.85; P < 0.001) and PFS (HR 0.84, 95% CI 0.79-0.89; P < 0.001). Conversely, females experienced a higher risk of grade ≥3 AEs (HR 1.12, 95% CI 1.07-1.18; P < 0.001).

Conclusions: In the largest analysis of IPD from trials supporting FDA drug approvals, we found that females had a 21% lower risk of death and a 16% lower risk of progression, but a 12% higher risk of severe adverse events. These findings highlight the value of the IPD sharing and the importance of sex-stratified evidence for risk stratification, dose optimisation and patient counselling.