Pyrotinib in Patients with HER2-Amplified Advanced Non–Small Cell Lung Cancer: A Prospective, Multicenter, Single-Arm Trial

作者：Zhengbo Song, Dongqing Lv, Shiqing Chen, Jianjin Huang, Yuping Li, Shenpeng Ying, Xiaoyu Wu, Feng Hua, Wenxian Wang, C. Xu, Ting Bei, Chan Gao, Zhijian Sun, Yiping Zhang, Shun Lü · 发表于：Clinical Cancer Research · 年份：2021 · DOI：10.1158/1078-0432.ccr-21-2936 · 被引用次数：56 · 研究领域：Lung Cancer Treatments and Mutations、HER2/EGFR in Cancer Research、Gastric Cancer Management and Outcomes

Abstract Purpose: In this study, we aimed to evaluate the efficacy and safety of pyrotinib, a pan-HER inhibitor, in patients with HER2-amplified non–small cell lung cancer (NSCLC). Patients and Methods: In this prospective, multicenter, single-arm trial (ChiCTR1800020262), patients with advanced NSCLC with HER2 amplification, as determined by next-generation sequencing, were enrolled and administered pyrotinib orally at 400 mg per day. The primary endpoint was 6-month progression-free survival (PFS) rate. Other endpoints included objective response rate (ORR), disease control rate (DCR), PFS, overall survival (OS), and safety. Results: The enrolled cohort included 27 patients with HER2 amplification. The 6-month PFS rate was 51.9% [95% confidence interval (CI), 34.0–69.3]. The median PFS (mPFS) was 6.3 months (95% CI, 3.0–9.6 months), and median OS was 12.5 months (95% CI, 8.2–16.8 months). Pyrotinib elicited a confirmed ORR of 22.2% (95% CI, 10.6%−40.8%). Patients administered pyrotinib as first-line treatment achieved an mPFS of 12.4 months. Moreover, 30.8% of the patients who had progressed on EGFR tyrosine kinase inhibitor (TKI) responded to pyrotinib. Patients with brain metastases had an ORR of 40%. Treatment-related adverse events (TRAE) occurred in all patients (grade 3, 22.2%), but no grade 4 or higher TRAEs were documented. Diarrhea was the most frequent TRAE (all, 92.6%; grade 3, 7.4%). Loss of HER2 amplification was detected upon disease progression. Conclusions: ...