Role of cachexia in advanced non-small cell lung cancer patients treated with EGFR-TKIS

Cachexia is a multifactorial syndrome associated with impaired physiologic reserve and adverse outcomes in advanced NSCLC. Its relationship with early toxicity and survival during EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy remains insufficiently characterized. We evaluated the impact of baseline cachexia on toxicity and clinical outcomes in patients with EGFR-mutated stage III–IV NSCLC treated with EGFR-TKIs. In this retrospective cohort, 247 consecutive patients treated with EGFR-TKIs were included. Cachexia was defined using the Fearon international consensus criteria. Hematologic and selected non-hematologic adverse events were recorded during the first four months of therapy. Associations with hematologic toxicity were assessed using logistic regression, and progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan–Meier methods and Cox regression. Baseline cachexia was present in 91 patients (37%). Cachectic patients more frequently had KPS <90 (44% vs 27%) and liver metastases (19% vs 5.8%). Overall hematologic toxicity was higher among cachectic versus non-cachectic patients (85.7% vs 69.9%), driven mainly by anemia (40% vs 21%) and lymphopenia (74% vs 56%). Cachexia independently predicted hematologic toxicity (adjusted OR 2.26, 95% CI 1.15–4.68) and worse OS (adjusted HR 1.65, 95% CI 1.07–2.57); median OS was 37.22 months in cachectic patients versus 45.80 months in non-cachectic patients. Baseline cachexia was associated with a higher burden of early hematologic toxicity and independently worse OS in EGFR-mutated advanced NSCLC treated with EGFR-TKIs. Routine baseline identification may help prioritize early supportive care and closer monitoring during the initial months of therapy.