Sex-based differences in clinical outcomes for solid tumours: A pooled IPD meta-analysis of contemporary anticancer drug trials.

Abstract

11042 Background: Sex-based differences in outcomes with contemporary oncology treatments remain underexplored, creating a gap in the evidence required for personalised care. To address this, our objective was to systematically evaluate whether sex differences exist in survival and adverse event outcomes with modern anticancer therapies. Methods: Individual patient data (IPD) was accessed via the Vivli platform from 60 clinical trials supporting US Food and Drug Administration approvals of anticancer medicines for the treatment of solid tumours from 2012 to 2022. Of these, 39 trials were included in analysing sex-based differences in clinical outcomes (i.e. breast, prostate, and ovarian cancer were excluded) Two-stage IPD meta-analysis approaches were employed. First, Cox proportional hazards models were applied to estimate hazard ratios (HRs) with confidence intervals for overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events (AEs) outcomes by sex within each clinical trial. Complete case analyses were conducted, with adjustments for covariates including age, race, ECOG performance status, and weight, as well as study-level factors, such as randomisation arm stratification. The results for each clinical trial were then pooled using random-effects meta-analysis. Subgroup analyses were performed to evaluate findings by cancer and treatment types. Results: Data from 39 trials for solid tumours (n=20,806; females=8,367) were analysed, including non-small cell lung (n=19), melanoma (n=6), colorectal (n=3), urothelial (n=2), gastric (n=2), and other (n=7) cancers. Treatment regimens evaluated included immunotherapies (n=9 trials), chemotherapies (n=18), and targeted therapies (n=32). In adjusted analyses, females demonstrated favourable OS (HR 0.78, 95% CI: 0.72–0.84; I² = 60%, p <0.001) and PFS (HR 0.84, 95% CI: 0.80–0.89; I² = 47%, p <0.001) compared to males. However, females had a higher risk of grade ≥3 AEs (HR 1.12, 95% CI: 1.05–1.18; I² = 40%, p <0.001). Subgroup analyses by cancer type and treatment regimen showed consistent trends in survival and AE outcomes according to sex. Conclusions: This meta-analysis, highlights consistency in females experiencing improved survival but higher toxicity compared to males with contemporary oncology treatments. These findings underscore the need to incorporate and prioritise sex as a key biological variable in trial design, dose optimisation, outcome analysis, and clinical decision-making within the oncology setting. Acknowledgement This publication is based on research using data from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly and Company, Hoffmann-La Roche, Janssen, Pfizer, Sanofi, and Takeda that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.