Anti-human epidermal growth factor receptor 2 (HER2) therapy is an effective treatment for HER2-positive gastric and breast malignancies. However, the efficacy of HER2-targeted therapy in non-small cell lung cancer (NSCLC) patients with HER2 alterations remains controversial. We searched studies on HER2-targeted therapy in NSCLC patients that reported objective response rate (ORR), disease control rate (DCR) and progressionfree survival (PFS) published from database inception to 30 May 2021. A total of 32 trials involving 958 patients were included. The ORRs of HER2-TKIs targeted therapy, humanised monoclonal antibody, trastuzumab-based treatment and antibody-drug conjugate (ADC) (T-DM1) were 22% (95% CI 11-31), 23% (95% CI 20-65), 26% (95% CI 14-39) and 16% (95% CI _6-37), while that of ADC (DS-8201) was 60% (95% CI 35-85). The DCRs of these groups were 59% (95% CI 49-69), 39% (95% CI _9-88), 63% (95% CI 37-89), 31% (95% CI 4-58) and 87% (95% CI 62-112), respectively. In the subgroup analysis, numerically higher ORRs and DCRs were observed in the poziotinib (38%; 75%) and pyrotinib (35%; 83%) groups. The median PFSs of these groups were 5.51 months, 3.09 months, 4.61 months, 2.65 months and 12.04 months, respectively. HER2-targeted therapy can be considered an acceptable treatment strategy for NSCLC patients with HER2 alterations. In particular, ADC (DS-8201), pyrotinib and poziotinib demonstrated promising anti-tumour activity in HER2-positive NSCLC.
Keywords: ERBB2; HER2; biomarkers; meta-analysis; non-small cell lung cancer; review; targeted therapy.
© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.