Abstract / Summary
For advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, targeted therapy is the standard first-line treatment, but acquired resistance and disease progression are inevitable. Identification of resistance mechanisms is crucial for guiding subsequent anti-tumor therapy. We report a 57-year-old female patient with advanced lung adenocarcinoma harboring an EGFR exon 21 L858R mutation. The patient experienced disease progression with rare gynecological metastasis after 16 months of first-line furmonertinib therapy. Next-generation sequencing (NGS) of the uterine metastatic lesion identified concurrence of EGFR mutation and ALK fusion, while fluorescence in situ hybridization (FISH) confirmed MET polysomy. The patient exhibited intolerance to the combination therapy of glumetinib plus furmonertinib. Subsequently, the patient received a combination of furmonertinib and the ALK-TKI ensartinib, which was assessed as a partial response (PR) at the first restaging evaluation (1 month after treatment initiation), with favorable safety and tolerability. Secondary ALK fusion may represent a rare but clinically meaningful resistance mechanism in EGFR-mutant NSCLC. Furthermore, while gynecological metastasis from lung cancer is uncommon, clinicians should be alert to this possibility in patients presenting with relevant symptoms, with pelvic examination conducted as needed.