Real-world outcomes of pembrolizumab-chemotherapy combination in metastatic non-small cell lung cancer by age and sex: A national population-based study.
This Australian retrospective population-based study of 4,782 adults with metastatic NSCLC found shorter real-world survival with pembrolizumab plus chemotherapy than reported in clinical trials, longer survival among females, and more frequent levothyroxine initiation among females.
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This Australian retrospective population-based study of 4,782 adults with metastatic NSCLC found shorter real-world survival with pembrolizumab plus chemotherapy than reported in clinical trials, longer survival among females, and more frequent levothyroxine initiation among females.
Research significance
The observed evidence suggests that sex may be associated with pembrolizumab-chemotherapy outcomes and thyroid-toxicity proxies in metastatic NSCLC; it remains an untested inference that biological sex could guide treatment selection or tailored toxicity monitoring, and the record provides no pediatric-specific evidence.
Source abstract
INTRODUCTION: Lung cancer is the leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) are standard first-line therapy for metastatic non-small cell lung cancer (NSCLC), but real-world outcomes in Australia are limited. MATERIALS AND METHODS: We conducted a retrospective, population-based cohort study using the Pharmaceutical Benefits Scheme and National Death Index data, accessed via the Australian Bureau of Statistics DataLab. Adults initiating pembrolizumab with chemotherapy between January 1, 2019, and June 30, 2023, consistent with KEYNOTE-189 and KEYNOTE-407 trial regimens, were included. Overall survival (OS) and time to treatment discontinuation (TTD) were evaluated using Kaplan-Meier methods and multivariable Cox regression. Immune-related adverse events (irAEs) were inferred from incident corticosteroid or levothyroxine prescriptions. Subgroup analyses were conducted by age (18-64 vs. ≥ 65 years) and sex. RESULTS: Among 4782 patients (KEYNOTE-189: n = 3638; KEYNOTE-407: n = 1144), median OS was 13.8 months in the KEYNOTE-189 cohort and 12.0 months in the KEYNOTE-407 cohort. Female patients had significantly longer OS than males in both cohorts. Median TTD did not differ significantly by age or sex. Levothyroxine initiation, used as a proxy for thyroid-related irAEs, was more frequent among female patients across both cohorts. DISCUSSION: In this nationwide cohort, real-world survival with pembrolizumab-chemotherapy was shorter than in clinical trials. Observed sex-based differences in survival and irAE proxies suggest potential biological variation in ICI response and toxicity. These findings highlight the value of population-level data to inform personalised, evidence-based immunotherapy in advanced NSCLC.