Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers
Diabetes Mellitus, Type 2
Polymorphism, Single Nucleotide
© 2019 American Cancer Society Background: Mutations in human epidermal growth factor receptor 2 (HER2; also known as ERBB2) are found in approximately 2% of lung adenocarcinomas. The frequency and clinical course of brain metastases in this oncogenic subset are ill defined. Methods: Baseline and subsequent development of brain metastases was evaluated in consecutive patients with HER2-mutant (n = 98), epidermal growth factor receptor (EGFR)–mutant (n = 200), and KRAS-mutant lung cancers (n = 200). Results: At metastatic diagnosis, the odds ratio (ORs) for brain metastases was similar for patients whose tumors harbored HER2 mutations (19%) in comparison with patients with KRAS mutations (24%; OR for HER2 vs KRAS, 0.7; P =.33) but lower compared to patients with EGFR mutations (31%; OR for HER2 vs EGFR, 0.5; P =.03). Patients with lung cancer and HER2 mutations developed more brain metastases on treatment than patients with KRAS mutations (28% vs 8%; hazard ratio [HR], 5.2; P <.001) and trended more than patients with EGFR mutations (28% vs 16%; HR, 1.7; P =.06). Patients with HER2 YVMA mutations also developed more brain metastases on treatment than patients with KRAS mutations (HR, 5.9; P <.001). The median overall survival (OS) was shorter for patients with HER2-mutant (1.6 years; P <.001) or KRAS-mutant lung cancers (1.1 years; P <.001) than patients with EGFR-mutant lung cancers (3.0 years). Brain metastases occurred in 47% of patients with HER2-mutant lung cancers, which imparted shorter OS (HR, 2.7; P <.001). Conclusions: These data provide a framework for brain imaging surveillance in patients with HER2-mutant lung cancers and underpin the need to develop HER2-targeted agents with central nervous system activity.
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