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01-12-2022 | NSCLC | Research article

Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial

Authors: Zhengbo Song, Yuping Li, Shiqing Chen, Shenpeng Ying, Shuguang Xu, Jianjin Huang, Dan Wu, Dongqing Lv, Ting Bei, Shuxun Liu, Xiaoping Huang, Congying Xie, Xiaoyu Wu, Jianfei Fu, Feng Hua, Wenxian Wang, Chunwei Xu, Chan Gao, Shangli Cai, Shun Lu, Yiping Zhang

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations.

Methods

In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored.

Results

Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2–60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2–30.0), with median PFS of 5.6 months (95% CI, 2.8–8.4), and median OS of 10.5 months (95% CI, 8.7–12.3). The median duration of response was 9.9 months (95% CI, 6.2–13.6). All treatment-related adverse events (TRAEs) were grade 1–3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression.

Conclusions

Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation.

Trial registration

Chinese Clinical Trial Registry Identifier: ChiCTR1800020262

Available only for authorised users

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Title: Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial
Authors: Zhengbo Song
Yuping Li
Shiqing Chen
Shenpeng Ying
Shuguang Xu
Jianjin Huang
Dan Wu
Dongqing Lv
Ting Bei
Shuxun Liu
Xiaoping Huang
Congying Xie
Xiaoyu Wu
Jianfei Fu
Feng Hua
Wenxian Wang
Chunwei Xu
Chan Gao
Shangli Cai
Shun Lu
Yiping Zhang
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: NSCLC
Tyrosine Kinase Inhibitors
NSCLC
Tyrosine Kinase Inhibitors
Afatinib
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-022-02245-z

ACC 2024 Congress

Springer Medicine

Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial

Abstract

Background

Methods

Results

Conclusions

Trial registration

ACC 2024 Congress

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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