Real-World Analysis of the Efficacy and Safety of a Novel Irreversible HER2 Tyrosine Kinase Inhibitor Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer

Ying Sun,1,2,* Beibei Chen,3,4,* Jisheng Li,3,* Ling Peng,5 Shuguang Li,3 Xuejun Yu,3 Li Li3 1Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China; 2Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, 266035, Shandong Province, People’s Republic of China; 3Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong Province, People’s Republic of China; 4Department of Radiation Oncology, Heze Municipal Hospital, Heze, 274031, Shandong Province, People’s Republic of China; 5Department of Respiratory Disease, Zhejiang Provincial People’s Hospital, Hangzhou, 310000, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Li; Xuejun YuDepartment of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Wenhua Xi Road 107, Jinan, 250012, Shandong Province, People’s Republic of ChinaTel +86 531-82169851Email drlili5060@163.com; yuxuejun@qiluhospital.comBackground: As a novel irreversible pan-ErbB inhibitor recently approved in China, pyrotinib has exhibited promising anticancer efficacy and acceptable safety profile in HER2-positive metastatic breast cancer (mBC). The aim of this retrospective study was to estimate the efficacy and safety of pyrotinib treatment in Chinese mBC patients.Methods: We retrospectively reviewed the real-world clinicopathological and treatment data of HER2-positive mBC patients receiving pyrotinib-based treatment from August 2018 to July 2019 in Qilu Hospital of Shandong University and other medical centers of Shandong Province in China.Results: A total of 64 patients treated with pyrotinib were included for analysis, and the median follow-up duration was 260 days (interquartile range, 199.0 to 339.0 days). Fifty-nine (92.2%) patients had been previously treated with trastuzumab and/or T-DM1, while 11 (17.2%) patients had been exposed to lapatinib. The objective response rate (ORR) of all patients was 73.4%, and the disease control rate (DCR) was 98.4%, with a clinical benefit rate (CBR) of 87.5%. Patients with exposure to lapatinib responded well to pyrotinib-based treatment, although the ORR was significantly lower compared with that of patients without exposure to lapatinib (44.1% vs 77.5%, p=0.037). Previous lapatinib exposure was negatively associated with the objective response of pyrotinib treatment (odds ratio [OR]=0.248, 95% confidence interval [CI] 0.063– 0.970, p=0.045). The median progression-free survival (mPFS) for patients with previous lapatinib exposure and patients with visceral metastasis was 299 days (95% CI 240.1– 357.9 days) and 359 days (95% CI 258.3– 459.7 days), respectively. But the mPFS of the whole cohort has not been reached until the cut-off date. Cox multivariate analysis revealed that only visceral metastasis was an independent predictor of significantly shorter PFS (p=0.041) but not previous exposure to lapatinib (p=0.092). Diarrhea (28.1%), hand-foot syndrome (17.2%), and neutropenia (9.4%) were the most common grade 3 adverse events associated with pyrotinib treatment.Conclusion: Pyrotinib is highly beneficial to HER2-positive metastatic breast cancer patients, even in patients with previous lapatinib exposure. Pyrotinib is a feasible replacement of lapatinib in combination with chemotherapeutic drugs or as a monotherapy. Adverse effects are tolerable and easily manageable.Keywords: breast cancer, HER2 positive, pyrotinib, adverse effect, objective response rate