Pyrotinib in <i>HER2</i>-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study.

Abstract

Targeted therapies against non-small-cell lung cancer (NSCLC) harboring <i>HER2</i> mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with <i>HER2</i>-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. Patients with stage IIIB or IV <i>HER2</i>-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different <i>HER2</i> mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% <i>v</i> 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with <i>HER2</i>-mutant NSCLC.