A multicentre, open-label, single-arm, phase II study, conducted in China explored the efficacy and safety of pyrotinib, an oral, irreversible, pan-ErbB tyrosine kinase inhibitor against HER1, HER2, and HER4 in patients with advanced non-small cell lung cancer (NSCLC) harbouring HER2 mutations, who had received at least one prior platinum-containing chemotherapy for advanced/metastatic disease. Caicun Zhou of the Shanghai Pulmonary Hospital, Tongji University School of Medicine in Shanghai, China and co-authors reported on 2 July 2020 in the Journal of Clinical Oncology that pyrotinib as a single agent showed a promising antitumour activity and an acceptable safety profile in that setting.
Combination of pyrotinib and capecitabine is approved in China for HER2-positive advanced breast cancer. A previous study demonstrated more favourable antitumour activity of pyrotinib than afatinib or T-DM1 in the patient-derived HER2-mutated lung cancer xenograft model.
Patients with HER2-mutated NSCLC account for 1-4% of patients with lung adenocarcinoma. The authors wrote in the study background that targeted therapies against NSCLC harbouring HER2 mutations remain an unmet need. In this study (NCT02834936), the Chinese investigators explored the efficacy and safety of pyrotinib in patients with advanced NSCLC and HER2 mutations who had received at least one prior platinum-containing chemotherapy for advanced/metastatic disease.
The investigators enrolled in this study the patients with stage IIIB or IV HER2-mutated lung adenocarcinoma who were previously treated with platinum-based chemotherapy. The primary endpoint was objective response rate (ORR) per independent review committee (IRC).
In total, 60 patients received pyrotinib. At baseline, 58 patients (96.7%) had stage IV disease; 25 patients (41.7%) received at least 2 lines of prior chemotherapy. As of data cut-off on 20 June 2019, IRC-assessed ORR was 30.0% (95% confidence interval [CI] 18.8% to 43.2%).
All subgroups of patients with different HER2 mutation types showed a favourable ORR. The ORRs were similar between patients with and without brain metastases (25.0% vs 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 diarrhoea (20.0%; all grade 3). No treatment-related deaths were reported.
A major limitation of this study is the lack of a control arm and the small sample size of patients with missense point mutation in HER2. Therefore, the authors were unable to adequately compare the clinical benefit of different subtypes in HER2 mutations.
A global, multicentre, randomised phase III trial is planned and will be started soon.
The authors concluded that it is the largest study in HER2-mutated NSCLC. Pyrotinib 400 mg daily could be given to patients with HER2-mutated advanced NSCLC, who had received at least one prior platinum-based chemotherapy. To avoid diarrhoea, the most common adverse event attributable to pyrotinib, the study team recommended prophylactic loperamide.
The study was supported by Jiangsu Hengrui Medicine Co, Ltd.
Zhou C, Li X, Wang Q, et al. Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study. JCO; Published online 2 July 2020. DOI: https://doi.org/10.1200/JCO.20.00297