Efficacy and Side Effects in HER2-Positive Advanced Breast Cancer Patients Treated with Pyrrotinib: A Real-World Study in China

Research Article

Ann Hematol Oncol. 2021; 8(9): 1366.

Efficacy and Side Effects in HER2-Positive Advanced Breast Cancer Patients Treated with Pyrrotinib: A Real-World Study in China

Xiaolei Wang¹, Chen Xu Meng², Jingjing Li¹, Yu Su³, Fanfan Li¹* and Jun Yang Zhao³*

1Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, China

2Department of Ophthalmology, Anhui Provincial Children’s Hospital, China

3Department of Pediatric Oncology Center, Beijing Children Hospital, Capital Medical University, China

*Corresponding author: Fanfan Li, Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230000, Anhui Province, China

Jun Yang Zhao, Department of Pediatric Oncology Center, Beijing Children Hospital, Capital Meidical University, National Center for Children’s Health, China

Received: June 21, 2021; Accepted: July 13, 2021; Published: July 20, 2021


Background: Pyrotinib is a molecular and irreversible tyrosine kinase inhibitor independently developed in China, and its efficacy against HER2- positive breast cancer in the real world is not clear. In this study, we evaluated the efficacy and safety of pyrotinib in the treatment of HER2-positive advanced breast cancer based on real-world evidence.

Materials and Methods: We designed a prospective observational study. Thirty-six patients with HER2-positive advanced breast cancer from a single medical center were included in the study from December 2018 to February 2021. All patients received the oral HER2 receptor inhibitor pyrotinib and received concurrent chemotherapy or endocrinotherapy. The follow-up endpoint is set as April 1, 2021. The primary endpoint is Objective Response Rate (ORR) and Disease Control Rate (DCR), and the secondary endpoint is Progression- Free Survival (PFS) and related side effects.

Results: By the end point of follow-up, a total of 17 patients had progressed (including 6 deaths), and the progression-free survival rate was 52.78%. The median PFS was 13months (PFS range: 3-22 months). As the best response, 4 patients achieved CR, 20 patients achieved PR, 9 patients achieved SD, and 3 patient developed PD. The ORR was 66.67% and DCR was 91.67%. In the analysis, first-line pyrotinib treatment appeared to have higher ORR (88.88% vs 59.26%), but there was no significant difference. In addition, pyrotinib showed significant efficacy in patients with brain metastases, with an ORR of 42.85%. In terms of safety, the incidence of diarrhea was 80.55%, but only 4 patients had grade 3 diarrhea, which was tolerable after the drug dose was reduced; 1 patient had grade 4 neutropenia and grade 3 and thrombocytopenia, which were considered to be related to the chemotherapy drugs. The incidence of other adverse reactions was low, and all were grade 1 to 2.

Conclusion: Pyrotinib combined with chemotherapy has a significant effect on HER2-positive breast cancer, and there is still a high ORR in patients who fail multiple lines of treatment. Side effects are overall controllable and safe.

Keywords: Breast neoplasms; Pyrotinib; Human epidermal growth factor receptor 2; Objective response rate; Disease control rate; Progression-free survival


Breast cancer is currently one of the most important and common malignant tumor diseases leading to female death worldwide [1], and the incidence is still increasing and showing a tendency to be younger [2]. Human Epidermal Growth Factor Receptor-2 (HER2) positive breast cancer is a pathological type with a very rapid progression of the disease, and its clinical manifestations are aggressive, prone to visceral and central nervous system metastases, and have a poor prognosis [3]. Anti-HER-2 therapy is currently the most important treatment for patients with HER-2 positive breast cancer in clinical practice. The study showed that the 5-year survival rate of HER2- positive breast cancer patients without anti-HER2 therapy was 13.2%; the absolute difference was 11.3% compared with HER2- negative patients [4]. With the clinical application of drugs such as trastuzumab [5], pertuzumab [6] and lapatinib [7], the situation has been greatly improved, of which trastuzumab is currently the firstline treatment for HER-2 positive advanced breast cancer patients [8,9]. However, anti-HER2 therapy after drug resistance remains a clinical challenge.

At present, the therapeutic drugs targeting HER2 in clinical practice include monoclonal antibodies, tyrosine kinase inhibitors and antibody drug conjugates. The marketed pyrotinib in 2018 is a multi-target tyrosine kinase inhibitor targeting HER1, HER2 and HER4 intracellular kinase regions independently developed in China. The current phase II and III clinical studies [10,11] have encouraging results. In the multicenter randomized controlled study of MA et al. [12], it was shown that pyrotinib combined with capecitabine had a high objective response rate of 78.5% and progression-free survival of 18.1 months in the treatment of HER2-positive advanced breast cancer. It is not difficult to find by reviewing the clinical study data that: the physical status of patients is relatively good (ECOG score 0~1); about 30% of patients experience only one chemotherapy after recurrence and metastasis, and nearly 50% of patients do not receive chemotherapy after recurrence and metastasis; the combined chemotherapeutic drugs are limited to capecitabine. At present, the treatment data of pyrotinib in the real world are limited. Considering that in clinical practice, no matter the performance status of patients, the times of chemotherapy, or the combination of chemotherapeutic drugs have different degrees of differences from clinical studies, we designed a prospective observational study to clarify the efficacy and safety of pyrotinib in the real world, in order to provide more reference for clinical practice.

Materials and Methods


A total of 36 patients with HER2-positive advanced breast cancer admitted from December 2018 to February 2021 were retrospectively analyzed. General information, pathology and immunohistochemistry, treatment process, imaging data during pyrotinib administration, and side effects were collected from the patients.

Treatment method

The initial dose of oral pyrotinib was 320 mg (increased to 400 mg/day if well tolerated) or 400 mg. The combination of capecitabine, submit, vincitabine, taxanes, cemorelbine and etoposide was used. For grade 1-2 adverse reactions, corresponding symptomatic treatment should be given without dose adjustment; if grade 3 or higher adverse reactions occur, the dose of pyrotinib or chemotherapeutic drugs should be reduced according to the specific type of adverse reactions.

Efficacy evaluation

According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, Complete Response (CR) is the disappearance of all target lesions; Partial Response (PR) is =30% decrease in the sum of the long diameters of baseline lesions; Stable Disease (SD) is a decrease in the sum of the long diameters of baseline lesions but without PR or increase but without progressive disease (PD); PD is an increase in the sum of the long diameters of baseline lesions of more than 20%, an increase in the minimum absolute value of 5 mm or the appearance of new lesions. Objective Response Rate (ORR): CR + PR, disease control rate (DCR): CR + PR + SD.

Assessment of adverse events (AEs)

The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC 4.0) was used for judgment, and the AEs were classified into grade 1~5.

Statistical analysis

SPSS 23.0 was used to statistically analyze the data: the enumeration data were expressed as an example (percentage) [n (%)], Χ2 test or Fisher’s exact test was performed, and the test level was a = 0.05; there was a significant difference in the evaluation results at P<0.05. Kaplan-Meier curves for patients’ PFS were plotted using GraphPad 7.0.


Patient baseline data

A total of 35 female patients and 1male with HER2-positive advanced breast cancer admitted from December 2018 to February 2021 were included, aged 29 to 82 years, the average age was 49 years old. 9 patients had ECOG score greater than 1. 20 patients had negative HR status. 19 patients had internal metastasis, 7 patients had central nervous system metastasis; the number of lines of anti-HER2 therapy with pyrotinib and the specific combination of chemotherapeutic drugs were 9 (Table 1).