Abstract
BackgroundHER2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy. The aim of this study was to investigate the efficacy of first line chemotherapy in patients with advanced HER2-mutant lung adenocarcinomas.MethodsPatients with advanced NSCLC(N = 1714) initially underwent testing for EGFR, KRAS, BRAF mutations and ALK, ROS1 rearrangements, and negative cases were then assessed for HER2 mutations using the method of amplification refractory mutation system(ARMS). The efficacy of first line pemetrexed-based chemotherapy was investigated in patients with HER2-mutant and those with EGFR-mutant, ALK/ROS1-rearranged and KRAS-mutant advanced adenocarcinomas.ResultsHER2 mutations were detected in 29 of 572(5.1%) specimens from a selected population of EGFR/KRAS/BRAF/ALK/ROS1 negative patients. All of them are adenocarcinomas. Among patients with HER2-mutant lung cancers, 25 received pemetrexed-based first line chemotherapy. The objective response rate(ORR) was 36.0%. Their median progression free survival(PFS) was 5.1 months, which was similar with that of KRAS-mutant group (n = 40,5.0 months, p = 0.971), numerically shorter than that of EGFR-mutant group(n = 74, 6.5 months, p = 0.247) and statistically significantly shorter than that of ALK/ROS1-rearranged group (n = 39,9.2 months, p = 0.004). Furthermore, HER2 variants subgroup analysis showed that PFS was inferior in A775_G776insYVMA group compared with other variants (4.2 vs 7.2 months, p = 0.085).ConclusionsPatients with advanced HER2-mutant lung adenocarcinomas showed an inferior outcome of first line pemetrexed-based chemotherapy compared to those with ALK/ROS1 rearrangements, which strengthen the need for effective HER2-targeted drugs in clinical practice.
Highlights
Human epidermal growth factor receptor2 (HER2) mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy
Patients’ characteristics From January 2015 to September 2016, a total of 1714 patients with advanced Non-small cell lung cancers (NSCLC) underwent testing for EGFR, KRAS, BRAF, ALK and ROS1.The results showed that there were 809 patients(47.2%) with EGFR mutations,149(7.8%) with KRAS mutations,19(1.1%) with BRAF mutations,106(6.2%) with ALK rearrangements, 43(2.5%) with ROS1 rearrangements, and 16 patients (0. 9%) with multiple positive results
Outcomes of chemotherapy: Comparison among oncogenic mutations groups Patients received first-line pemetrexed-based chemotherapy were eligible for analysis(n = 25,14 combined with carboplatin, 7 combined with cisplatin and 4 monotherapy)
Summary
HER2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers(NSCLC) and HER2-directed therapies have shown promising results in this unique population, while little is known about its association with outcomes of chemotherapy. The aim of this study was to investigate the efficacy of first line chemotherapy in patients with advanced HER2-mutant lung adenocarcinomas. Human epidermal growth factor receptor2(HER2) positivity is well-studied in breast cancer, while much less defined in lung cancer. Wang et al BMC Cancer (2018) 18:326 target HER2 gene mutations are currently being investigated. The National Comprehensive Cancer Network (NCCN) recommend trastuzumab or afatinib as potential therapy options for non-small cell lung cancers(NSCLC) patients with HER2 mutations. HER2 mutation is emerging as a promising druggable target, while the optimal choice of targeted therapy remains poorly defined
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