Sex disparities in advanced non-small cell lung cancer survival: A Danish nationwide study

Abstract

Background

Historically, cancers often exhibit sexual dimorphism. However, following the introduction of immune checkpoint inhibitors and targeted therapies into routine clinical practice, the association of sex on patient and tumour characteristics, as well as survival remains largely unexplored in advanced NSCLC.

Patients and methods

In this observational study, we identified adults diagnosed with advanced NSCLC from January 1, 2017, to December 31, 2023, using Danish nationwide health registries and clinical databases. We compared females to males across demographic, social, socioeconomic, patient and tumour characteristics (including PDL-1 expression and driver mutations), treatments, and overall survival (OS) from diagnosis and initiation of the first line of treatment (LOT1). Cox proportional hazards regression was employed, adjusting for key covariates in the overall cohort and stratified by stage, histological subtype, PD-L1 expression level, and treatment type. Propensity score matching was conducted as a sensitivity analysis.

Results

Among 14,635 included individuals, males comprised 50 % (n = 7,322). Patient and tumour characteristics differed between sexes. The crude and adjusted female-to-male mortality hazard ratio (HR) was 0·82 (95 % confidence interval [CI]: 0·79–0·85) and 0·84 (0·81–0·88) from diagnosis and 0·80 (0·76–0·84) and 0·80 (0·75–0·84) from initiation of LOT1. Median OS for females and males was 8·8 months (95 % CI 8·4–9·2) and 7·0 months (6·7–7·3) from diagnosis and 14·1 months (13·5–15·1) and 10·9 months (10·3–11·5) from initiation of LOT1. Stratified analyses revealed that across all strata, females consistently demonstrated either favourable or comparable outcomes compared to males.

Conclusions

This study increases our understanding of sex-based disparities in advanced NSCLC. Adjusted analyses addressing previously suggested explanations for sex disparities in survival still demonstrated a longer survival for females, indicating yet-unidentified sex differences with potential clinical implications. Our results underscore the critical role of acknowledging sex as a key variable in oncology trials, research, and clinical practice.