# Sex-specific efficacy and safety outcomes in patients with resectable stage III non-small-cell lung cancer (NSCLC) undergoing neoadjuvant therapies: a pooled analysis of the SAKK trials 16/96, 16/00, 16/01, 16/08 and 16/14

## TL;DR

Female patients with stage III lung cancer had better survival outcomes than males, likely due to lower non-cancer-related deaths.

## Contribution

This study identifies sex-based survival differences in stage III NSCLC patients undergoing neoadjuvant therapies.

## Key findings

- Female patients had significantly longer event-free and overall survival compared to males.
- Male patients had a higher risk of non-cancer-related deaths.
- Treatment-related severe adverse events were similar between sexes.

## Abstract

Current data suggest better survival in various cancer types but increased treatment toxicity in female compared with male patients. In this article, we report a pooled analysis of sex-related differences in survival outcomes and safety in patients with resectable stage III non-small-cell lung cancer (NSCLC) treated in five prospective clinical trials.

Data from 499 patients included in five Swiss Group for Clinical Cancer Research (SAKK) trials for resectable stage III NSCLC were pooled. All patients were treated with three cycles of chemotherapy (cisplatin/docetaxel), either alone (n = 207, 41%), with sequential radiotherapy (n = 229, 46%) or with sequential perioperative programmed death-ligand 1 blockade (n = 62, 12%).

Of 499 patients included, 341 (68.3%) were male. Median event-free survival (EFS) [24.4 versus 11.8 months, hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.06-1.64, P = 0.014] and median overall survival (OS) (59.3 versus 26.1 months, HR 1.45, 95% CI 1.15-1.83, P = 0.0018) were significantly longer in female patients compared with male patients. OS/EFS remained significant in a multivariable Cox regression model. While the cause-specific hazard of non-cancer-related death was increased in males (HR 2.14, 95% CI 1.32-3.46, P = 0.0019), the risk of tumor-related death was not significantly different between sexes (HR 1.26, 95% CI 0.96-1.65, P = 0.09). No significant differences in treatment-related grade ≥3 adverse events (62.5% versus 69.7%) or treatment discontinuation (3.2% versus 3.2%) were observed.

In this pooled analysis, female patients with resectable stage III NSCLC had longer EFS and OS than males, mainly due to lower non-cancer-related mortality. Given the retrospective design and limited sample size, these results should be interpreted with caution. Prospective studies are needed to confirm these findings and explore underlying causes of sex-based differences.

•Females with resectable stage III NSCLC treated with neoadjuvant therapies have longer OS and EFS.•Severe treatment-related toxicities do not differ significantly between sexes.•Male patients have a higher risk of non-cancer-related deaths than females.

Females with resectable stage III NSCLC treated with neoadjuvant therapies have longer OS and EFS.

Severe treatment-related toxicities do not differ significantly between sexes.

Male patients have a higher risk of non-cancer-related deaths than females.