Comparable clinical outcomes in patients with HER2-mutant and EGFR-mutant lung adenocarcinomas

HER2 is a major proliferative driver in lung cancer. HER2 gene aberrations impact the prognosis of lung adenocarcinoma (ADC). A one-step reverse transcription-polymerase chain reaction was performed using RNA samples from 888 Asian lung cancer patients to detect HER2, EGFR, KRAS, ALK, and ROS1 mutations. The demographic data and treatment outcomes of HER2 mutation-positive lung ADC patients were analyzed and compared to those with HER2 mutation-negative tumors. HER2 mutation was identified in 40 (4.5%) lung ADC patients. HER2 mutations tended to occur in male patients with advanced-stage disease and never-smokers. A775_G776insYVMA (n=22, 55%) was the most prevalent HER2 mutation, followed by P780_Y781insGSP (n=4, 10%). For patients diagnosed with stage-IIIB/IV disease, HER2-mutant patients showed clinical outcomes comparable to EGFR-mutant patients (P=0.721, log-rank test) and a better overall survival (OS) compared to patients lacking driver mutations in the investigated genes (P=0.033, Breslow test). Specifically, lung ADC patients with stage-IV HER2-mutant tumors treated with chemotherapy or targeted agents, even without afatinib or anti-HER2 targeted therapy, showed similar clinical outcomes to lung ADC patients harboring EGFR exon 19 deletion or L858R mutations (P=0.870). In addition, multivariate analysis indicated that HER2 mutation status was not a major risk factor for diminished OS in stage-IV lung cancer. In conclusion, lung ADC harboring HER2 mutations showed distinct characteristics from other driver mutations, including increased chemosensitivity with in advanced stage disease.