Real-world clinical characteristics and outcomes in patients with HER2-mutant non-small cell lung cancer (NSCLC) who received second-line treatment: A nationwide database analysis in Japan

Background Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have been approved for HER2 -mutant NSCLC, real-world outcome data especially in the second-line setting remains limited. Methods This non-interventional study utilized the Center for Cancer Genomics and Advanced Therapeutics national database to identify patients with HER2 -mutant NSCLC who received second-line treatment in Japan. The primary objective was to characterize this population. Secondary objectives included describing second-line treatments and clinical outcomes (overall response rate [ORR], disease control rate [DCR], time on treatment [ToT] and reasons for second-line treatment termination). Results Among 3012 NSCLC patients identified, 168 (5.6%) had a HER2 mutation. In all NSCLC and HER2 -mutant patients, median age was 66.0 years; 38.1% and 53.6% were female; 68.2% and 42.3% had a history of smoking; and 25.8% and 31.0% had brain metastases. In HER2 -mutant patients, use of molecular targeted therapy (MTT, 44.6%) and chemotherapy (36.9%) as second-line treatment were comparable, followed by immunotherapy (15.5%), and immunochemotherapy (3.0%). Overall, median ToT with second-line treatment was 4.8 months (95% CI: 4.1–6.2). The longest median ToT was observed with MTT (8.1 months, 95% CI: 4.8–9.7), followed by chemotherapy (3.9 months, 95% CI: 2.5–5.2), immunochemotherapy (3.2 months, 95% CI: 0.4–not reached) and immunotherapy (5.5 months, 95% CI: 3.8–8.5). The ORR was 33.1% (95% CI: 25.4–41.6) and DCR was 78.4% (95% CI: 70.6–84.9). Conclusions MTT was the most common second-line treatment, however, outcomes were generally poor, emphasizing the unmet need for effective second-line treatments for HER2 -mutant NSCLC