目的:Pyrotinib是一种新型的不可逆酪氨酸激酶抑制剂,已显示出对人类表皮生长因子受体2(HER2)阳性转移性乳腺癌(MBC)的疗效。本研究探讨了在现实世界中吡唑替尼治疗HER2阳性MBC患者的疗效和安全性。
方法:从2018年9月至2022年2月,本研究纳入了在该中心治疗的137例HER2阳性MBC女性患者。随访期于2023年1月12日结束。这项研究的主要终点是无进展生存期(PFS)。总生存期(OS),客观反应率(ORR),疾病控制率(DCR),临床获益率(CBR),中枢神经系统(CNS)-PFS,CNS-ORR,CNS-CBR,CNS-DCR,和不良事件(AE)是次要终点。
结果:ORR,DCR和CBR分别为41.98%(55/131),87.79%(115/131)和44.27%(58/131),分别。该队列的中位PFS为10.37个月[95%置信区间(CI):9.205-11.535],中位OS为37.53个月(未达到)。单变量和多变量分析表明,曲妥珠单抗敏感性是改善PFS[风险比(HR):0.579(0.371-0.904,p=0.016)]和改善OS[0.410(0.213-0.790,p=0.008)]的独立预测因子。二线和三线或二线治疗的患者接受基于吡唑替尼的方案治疗的患者PFS较差[二线:3.315(1.832-6.000,p<0.001);三线或二线治疗:3.304(1.749-6.243,p<0.001)]和OS[二线治疗:4.631(1.033-20.771,p=0.045];三线治疗或二线治疗后(1.7212-174)这项研究中有38例脑转移(BM)患者,CNS-mPFS[14.37个月(7.815-20.925)与7.83个月(7.047-8.613),p=0.375]和mOS[未达到与36.40个月(18.551-54.249),p=0.034]脑放疗(BRT)组优于NBRT组。18.98%(26/137)的患者经历了3级或更高的腹泻。未报告AE相关死亡。
结论:这项研究证实了现实世界中基于吡罗替尼的治疗HER2阳性MBC患者的有希望的抗肿瘤活性和可接受的安全性。特别是那些对曲妥珠单抗敏感的患者,以及正在接受以吡rotinib为基础的方案作为高级一线治疗的患者.也已经证明,这些方案与BRT相结合,为这些BM患者提供更好的颅内反应和长期生存获益。
Pyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy 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 in the real world.
From September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center 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.
The ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p<0.001); third-or-post-line: 3.304 (1.749-6.243, p<0.001)] and OS [second-line: 4.631 (1.033-20.771, p=0.045); third-or-post-line: 5.738 (1.212-27.174, p=0.028)]. There were 38 brain metastases (BM) patients in this study, the CNS-mPFS [14.37 months (7.815-20.925) vs. 7.83 months (7.047-8.613), p=0.375] and mOS [not reached vs. 36.40 months (18.551-54.249), p=0.034] were better in brain radiotherapy (BRT) group than NBRT group. 18.98 % (26/137) of patients experienced grade 3 or higher diarrhea. No AE-related death was reported.
This study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.