Clinical Characteristics And Treatments Of HER2(ErbB2)-positive Non-small Cell Lung Cancer

Objective:To investigate the clinical characteristics of human epidermal growth factor receptor 2(HER2 or ErbB2)-positive non-small cell lung cancer(NSCLC)patients and the responses to various treatments,so as to explore the right treatment options in this subgroup of patients.Methods:Six cases of HER2-positive NSCLC patients in The First Affiliated Hospital of Soochow University from June 1,2014 to January 1,2018 were retrospectively analyzed.Medical records and telephone follow-up were used to analyze the patients’clinical characteristics,the changes of tumor markers,the gene detection results and responses to chemotherapies,antiangiogenic therapy,targeted therapy.Results:The mean age of the six cases of HER2-positive NSCLC patients was 62.2±8.5 years old.Women,non-smokers accounts for three cases(50%),four cases(67%),respectively.Four cases(67%)of primary lesions located in the right lung.Most patients were diagnosed by surgery(three cases,50%),with one case(17%)by fiberoptic bronchoscopy biopsy,one case(17%)by percutaneous lung biopsy and the other one(17%)by bronchoalveolar lavage fluid.All of the tumors’ pathological type is adenocarcinoma in five patients with confirmed pathological type.The gene detections were assessed in all six cases,using next generation sequencing(NGS)technology,with HER2 mutations in five patients and HER2 amplification in one patient.Two of these patients were detected positive together with PIK3CA,SMARCA4,TP53 mutations and BRCA2,PTEN,PDGFRA mutations,respectively.Overall survival(OS)of three cases in all the HER2-positive NSCLC patients was 36.0,24.0,1.0 months,respectively.While the other three patients who are still alive were followed up for 46.7,11.0,and 4.4 months,respectively.During the courses of the treatments of each patient,the trend of positive detection of respiratory tumor markers CA72-4,CYFRA211,NSE,CEA,CA125)was roughly consistent with the disease progression.Two patients received pemetrexed plus platinum chemotherapy in the first-line treatment,and the progression free survival(PFS)was 4.5 and 6.7 months,respectively.PFS of one patient who received bevacizumab as antiangiogenic therapy combined with cross-line chemotherapies in the third-line treatment was 10.1 months.For four patients using the first-line or second-line targeted therapy with afatinib,PFS of three patients were 8.6,3.0,3.9 months,respectively.The other one died from acute exacerbation of chronic obstructive pulmonary disease and respiratory failure 1.0 month after the targeted therapy while the effect could not be evaluated.There was also one case who was treated with afatinib as a posterior-lineEGFR tyrosine kinase inhibitors[J].Cancer Cell,2006,10(1):25-38.treatment,but she could not tolerate the adverse events(AEs)during the treatment and withdrawed,showing no clinical benefits.Conclusion:1.Primary HER2 mutations and amplifications are rare in patients with NSCLC.Most patients are non-smokers and the pathological type is mostly adenocarcinoma.The primary HER2 mutations are more common than the amplifications,and the incidence of HER2 positive combined with one or more gene abnormalities is high(2/6).2.At present,the first-line treatment chosen for HER2-positive advanced NSCLC patients is platinum-based doublet chemotherapy.Antiangiogenic therapy or trastuzumab combined with chemotherapy may achieve better results by synergistic effects..3.Afatinib as the targeted therapy in HER2-positive NSCLC patients has shown some effects in the first-line and second-line treatments.However,it may not show clinical benefits due to serious AEs in posterior-line treatments.4.In order to achieve the best treatment of HER2-positive NSCLC patients,larger clinical samples need to be explored in the future by NGS testing.