Abstract
Background: HER2 mutation is found in 1-2% of lung cancer patients. Chemotherapy remains the standard of care for patients harboring HER2 mutations, while many HER2 targeted tyrosine kinase inhibitors (TKIs) have been applied to them in practice in recent years. Studies comparing chemotherapy to HER2-TKIs were limited. This study was aimed to investigate the molecular and clinical patterns of HER2 mutations in advanced non-small cell lung cancer, and compare the different outcomes between chemotherapy and HER2-TKIs.
Methods: Advanced or recurrent non-small cell lung cancer patients with de novo HER2 mutations (N=75) were included in this study. Molecular information, clinical features, and treatment outcomes were retrospectively collected from a web-based patient registry and hospital chart review.
Results: Between October 2012 and December 2018, 65 patients with in-frame insertion mutations, 8 with point mutations and 2 with gene amplification were found. The most common subtypes of insertion mutations were A775_G776insYVMA, G776delinsVC, and V777_G778insGSP. HER2 mutated patients were mostly young-aged, females, never or light smokers, and adenocarcinoma. For HER2 mutated advanced NSCLC, chemotherapy achieved better outcomes than HER2-TKIs (median PFS: 5.5 vs 3.7 months in the first line setting and 4.2 vs 2.0 months in the second line setting, P=0.001 and 0.031, respectively). Especially for the most common subtype, YVMA insertions, PFS was significantly longer in chemotherapy than HER2-TKIs both in the first line (6.0 vs 2.6 months, P=0.008) and the second line (4.2 vs 2.6 months P<0.001).
Conclusions: HER2 mutated lung cancer patients were younger, mostly females, never or light smokers, histologically adenocarcinomas dominated. Compared to existed HER-TKIs, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype.
Trial registration: ChiCTR1800017709. Registered 10 August 2018.
MA14.06 Nintedanib-Docetaxel in 2nd Line Treatment in No Squamous Non-Small Cell Lung Cancer Patients, Refractory to First Line Treatment (GFPC02-15)
