Real-World Patient Characteristics, Mutational Landscape, and Outcomes in Advanced/Metastatic HER2 -Mutant Non–Small Cell Lung Cancer

PURPOSE This observational study assessed the real-world characteristics, treatments, and outcomes of US patients with HER2 -mutant advanced non–small cell lung cancer (NSCLC) overall and according to HER2 mutation type (tyrosine kinase domain [TKD] and non-TKD). METHODS Deidentified data were extracted for patients with advanced/metastatic NSCLC from the Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic Database. Patients with oncogenic HER2 mutations were included. The primary objectives were to assess the prevalence of HER2 mutations and coaberrations, treatment patterns, and real-world overall survival (OS). RESULTS Overall, 559/14,768 (3.8%) patients had HER2 mutations; 262 (1.8%) were oncogenic. Patients with oncogenic TKD mutations (n = 197) were more frequently younger, female, and never-smokers than those with oncogenic non-TKD mutations (n = 65) and had fewer oncogenic coaberrations. Among patients with oncogenic HER2 mutations who underwent first-line treatment (n = 193), most received platinum-based chemoimmunotherapy (30.5%) or chemotherapy alone (27.9%); 119 patients (61.7%) received second-line treatment. Median OS after first and second lines of treatment was 13.5 months (95% CI, 11.6 to 16.9) and 11.1 months (95% CI, 9.2 to 13.6), respectively. Median OS with first-line platinum-based chemoimmunotherapy was 21.1 (95% CI, 12.2 to NA) and 11.7 months (95% CI, 8.3 to NA) in patients with TKD/non-TKD mutations, respectively, and median OS with platinum-based chemotherapy alone was 9.1 (95% CI, 5.7 to 16.0) and 17.3 (95% CI, 13.6 to NA) months, respectively. CONCLUSION NSCLC patients with oncogenic TKD HER2 mutations had different characteristics and genetic features than patients with non-TKD mutations. Real-world outcomes with first- and second-line standard-of-care treatment were suboptimal, highlighting the need for new treatment options for patients with advanced HER2 -mutant NSCLC.