Abstract
BACKGROUND: Pyrotinib, a novel irreversible epidermal growth factor receptor 2 (EGFR)/HER2 dual tyrosine kinase inhibitor, has shown promising antitumor efficacy with tolerable toxicity in HER2-positive metastatic breast cancer (MBC) in several clinical trials. However, the clinical trials do not usually well reflect the patients in real clinical settings. Despite several small-sample studies in real world, the data on pyrotinib as first-line and third-or-later-line treatment and the efficacy comparison of pyrotinib combined with different regimens are still lacking. Therefore, this study aimed to investigate the efficacy and safety of pyrotinib for the HER2-positive MBC in real world to replenish more comprehensive data. METHODS: A total of 172 HER2-positive MBC patients treated with pyrotinib-based therapy were recruited from multiple centers in nonclinical trial settings from September 2017 to June 2020. RESULTS: The median progression-free survival (mPFS) of 172 patients was 8.83 months. The patients, receiving first-line pyrotinib treatment, had the longest mPFS (20.93 months) compared with those receiving second-line (8.67 months, p = 0.0339) and third-or-later-line (7.13 months, p = 0.0075) treatments, respectively. Prior treatment with lapatinib (p = 0.012) and site of metastasis (visceral vs. nonvisceral) (p = 0.033) were the independent prognostic factors for PFS. The prior treatment with lapatinib compared with lapatinib-native treatment (5.96 vs. 10.97 months, p = 0.0036) and those with visceral metastasis compared with nonvisceral metastasis (8.40 vs. 23.70 months, p = 0.0138) had worse mPFS. Among 146 patients evaluated for efficacy, 2.1%, 58.9%, and 32.9% showed complete response, partial response, and stable disease, respectively. Adverse events occurred in 92.4% of the patients with 33.3% Grade 3 and higher adverse events and diarrhea (57.0%), anemia (44.8%), and leukopenia (40.7%) as the most frequent ones. CONCLUSIONS: Pyrotinib-containing regimen could effectively treat HER2-positive MBC with acceptable toxicity, including the patients who progressed after lapatinib treatment and with brain metastasis.