Sarcopenia Predicts Outcome After Chemoimmunotherapy, Not Chemotherapy, in Advanced Lung Cancer: Single-Centre Retrospective Study

Abstract

Background Sarcopenia, characterized by progressive loss of skeletal muscle mass, is prevalent in patients with non-small cell lung cancer (NSCLC). While sarcopenia has been associated with poor prognosis in multiple types of cancer, its predictive role in the context of first-line treatment combining PD-(L)1 inhibitors with platinum-based chemotherapy (CITx) remains unclear in advanced NSCLC.Methods In a single-centre retrospective cohort, patients with advanced NSCLC without actionable genomic alterations who received either CITx (n = 552) or platinum-doublet chemotherapy alone (CTx; n = 622) were analysed. Sarcopenia was defined on the Martin's computed tomography-derived skeletal muscle index definition. Progression-free survival (PFS) and overall survival (OS) were assessed. Interaction between sarcopenia and treatment modality was explored.Results Sarcopenia was observed in 49.5% of patients. The presence of sarcopenia was associated with worse outcomes in overall patients (median OS: 9.4 vs. 11.4 months; HR 1.22, 95% CI 1.08-1.39). When stratified by treatment groups, sarcopenia was significantly associated with higher risk of progression (adjusted HR 1.23, 95% CI 1.01-1.49) and death (adjusted HR 1.42, 95% CI 1.16-1.74) in CITx-treated patients, whereas no such association was observed in the CTx group. The interaction between sarcopenia and treatment type was significant for both PFS (p = 0.041) and OS (p = 0.022).Conclusions Sarcopenia is a predictive biomarker for inferior outcomes in patients with advanced NSCLC treated with CITx, but not with CTx. Assessment of skeletal muscle mass can help identify patients at risk for suboptimal response to CITx. This study provides grounds for future exploration in interventions targeting sarcopenia and cachexia to enhance clinical outcomes in advanced cancer patients.