| Objective: Pyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)positive metastatic breast cancer(MBC).This study explored the efficacy and safety of pyrotinib in the treatment of HER2 positive MBC patients and with brain metastases patients in real-world.Methods: From September 2018 to February 2022,137 female patients with HER2 positive MBC treated in the Third Affiliated Hospital of Kunming Medical University were enrolled in this study.The follow-up period ended on January 12,2023.The primary endpoint of this study was progression-free survival(PFS).Overall survival(OS),objective response rate(ORR),disease control rate(DCR),clinical benefit rate(CBR),central nervous system(CNS)-PFS,CNS-ORR,CNS-CBR,CNS-DCR,and adverse event(AE)were the secondary endpoints.Results: 27.01%(37/137),35.76%(49/137),and 37.23%(51/137)of patients in this cohort were treated with pyrotinib-based regimens as advanced first-line,second-line,and third-or-post-line therapy,respectively.92.70%(127/137)of patients received pyrotinib in combination with other agents,of which 68.50%(87/127)were combined with chemotherapy,and capecitabine was the most commonly used combination chemotherapy agent.The ORR,DCR and CBR analysis included 131 patients with measurable lesions,and ORR,DCR and CBR were 41.98%(55/131),87.79%(115/131)and 44.27%(58/131),respectively.Patients treated with pyrotinib-based regimens as first-line had higher ORR(63.64% vs.40.43% vs.29.41%,p=0.008),DCR(96.97% vs.87.23% vs.82.35%,p=0.113),and CBR(81.82% vs.27.66% vs.35.29%,p<0.001)than those treated as second-line and third-or-post-line.The median duration of follow-up for the 137 patients was 22.17,the median PFS for this cohort was 10.37 months [95% confidence interval(CI): 9.205-11.535] and median OS was37.53 months(95%CI: not reached).Univariate and Multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio(HR): 0.579,95%CI:0.371-0.904,p=0.016] and improved OS(HR:0.410,95%CI:0.213-0.790,p=0.008).The use of pyrotinib-based regimens as second-line and third-or-post-line treatment were poor independent predictors of PFS(second-line:HR=3.315,95%CI: 1.832-6.000,p<0.001;third-or-post-line: HR=3.304,95%CI:1.749-6.243,p<0.001)and OS(HR=4.631,95%CI: 1.033-20.771,p=0.045;HR=5.738,95%CI: 1.212-27.174,p=0.028).There were 38 patients with brain metastases in this study,39.47%(15/38)of patients were combined with brain radiotherapy(BRT)during treatment with pyrotinib,of which eleven patients were combined with whole brain radiotherapy and four patients were combined with stereotactic radiotherapy.60.53%(23/38)of patients were not combined with BRT during treatment with pyrotinib.The CNS-ORR,CNS-DCR and CNS-CBR were higher in patients combined with BRT than in those combined without BRT.The CNS-m PFS [14.37months(95%CI: 7.815-20.925)vs.7.83months(95%CI:7.047-8.613),p=0.375] and m OS [not reached vs.36.40months(95%CI:18.551-54.249),p=0.034] were better in the combined with BRT group than in the combined without BRT group.Diarrhea was reported almost in all patients,with18.98%(26/137)of patients experienced grade 3 or higher diarrhea.Other grade 3 or higher adverse events were hand-foot syndrome(3.65%),leukopenia(2.19%)and an increased ALT/AST(1.46%).No AE-related deaths were reported.Conclusion: This study confirmed the efficacy as well as the safety of pyrotinib in the treatment of HER2 positive MBC in real-world,particularly in patients with trastuzumab sensitivity and used pyrotinib-based regimens as advanced first-line treatment.It also confirmed that a pyrotinib-based regimen combined with BRT resulted in better intracranial response and survival benefit for patients with brain metastases. |
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