Abstract
Entrectinib, a first-generation TRK inhibitor, is effective in NTRK fusion-positive non-small cell lung cancer (NSCLC) but commonly induces significant weight gain. We describe the case of a 42-year-old patient with metastatic NTRK-positive NSCLC undergoing entrectinib who participated in a two-year, supervised exercise program. The intervention included twice-weekly aerobic and resistance training aligned with international exercise-oncology guidelines. Adherence was high (91.6%), and no exercise-related adverse events occurred. Despite an initial 13 kg weight gain over 9 months, split between fat and lean mass, subsequent fat loss (~3.5 kg) occurred while lean mass was preserved. This case suggests that prolonged, structured exercise is a safe and feasible strategy to attenuate entrectinib-associated metabolic effects and support physical function during targeted therapy in advanced NSCLC.