Cancer Cachexia Predicts Benefit of Immunotherapy Plus Chemotherapy in EGFR-mutant NSCLC After TKI Resistance

Background/Aim: Cancer cachexia, characterized by weight loss and systemic inflammation, has been associated with poor prognosis in non-small cell lung cancer (NSCLC). However, its impact on treatment outcomes in tumors with mutant epidermal growth factor receptor (EGFR) remains unclear. This multicenter retrospective cohort study evaluated the impact of cancer cachexia on treatment selection after the development of resistance to EGFR tyrosine kinase inhibitors (TKIs). Patients and Methods: This study included 439 patients with advanced EGFR-mutant NSCLC who received chemotherapy (n=304) or immune checkpoint inhibitors (ICIs) combined with chemotherapy (n=135) after EGFR-TKI failure. Cancer cachexia was diagnosed based on specific weight loss criteria and laboratory data. Propensity score matching was performed to adjust for baseline differences, and survival outcomes were compared. Results: Overall, significant differences in treatment outcomes were observed between the groups. In the chemotherapy group, cancer cachexia was an independent predictor of overall survival (hazard ratio=1.53; p=0.004), whereas it was not associated with survival in the ICIs/chemotherapy group. Among patients with cachexia, overall survival was significantly longer with ICIs/chemotherapy than with chemotherapy alone (13.8 vs. 11.2 months; p=0.049). Conclusion: Although no significant survival difference was found between chemotherapy and ICIs/chemotherapy in the overall population, ICIs/chemotherapy conferred a survival benefit to patients with cancer cachexia. These findings suggest that the presence of cachexia may serve as a potential biomarker for treatment selection in EGFR-TKI-resistant, EGFR-mutant NSCLC.