评估吡咯替尼（一种不可逆泛 HER（人表皮生长因子受体）抑制剂）、曲妥珠单抗和多西他赛与安慰剂、曲妥珠单抗和多西他赛相比，对于未经治疗的 HER2 阳性转移性乳腺癌的疗效和安全性。随机、双盲、安慰剂对照、多中心、3 期试验。2019 年 5 月 6 日至 2022 年 1 月 17 日期间，中国 40 个中心研究了 590 名未经治疗的 HER2 阳性转移性乳腺癌女性患者（中位年龄 52（四分位距 46-58）岁）。符合条件的患者按 1:1 随机分配接受口服吡咯替尼（每天一次 400 毫克）或安慰剂，并在每 21 次治疗的第一天联合静脉注射曲妥珠单抗（第 1 周期为 8 毫克/公斤，后续周期为 6 毫克/公斤）和多西紫杉醇（75 毫克/平方米）日循环。根据（新）辅助治疗中曲妥珠单抗的治疗史和激素受体状态对随机分组进行分层。患者、研究者和申办者的研究团队对治疗分配情况不知情。主要终点是研究者评估的无进展生存期。在 590 名随机患者中，297 名接受了吡咯替尼、曲妥珠单抗和多西紫杉醇治疗（吡咯替尼组），并且293 人接受安慰剂、曲妥珠单抗和多西他赛治疗（安慰剂组）。截至 2022 年 5 月 25 日数据截止，中位随访时间为 15.5 个月。根据研究者的说法，吡咯替尼组的中位无进展生存期显着长于安慰剂组（24.3（95% 置信区间 19.1 至 33.0）个月 vs 10.4（9.3 至 12.3）个月；风险比 0.41（95% 置信区间）区间0.32至0.53）；单侧P<0.001）。吡咯替尼组 297 名患者中有 267 名（90%）报告了 3 级或以上治疗相关不良事件，安慰剂组 293 名患者中有 224 名（76%）报告了治疗相关不良事件。吡咯替尼组未发生治疗相关死亡，安慰剂组发生 1 例（<1%；糖尿病高渗性昏迷）治疗相关死亡。生存和毒性仍在评估更长的随访时间。与安慰剂、曲妥珠单抗和多西他赛相比，吡咯替尼、曲妥珠单抗和多西他赛在未经治疗的 HER2 阳性转移性乳腺癌患者中显示出优越性，可显着改善无进展生存期。毒性是可控的。研究结果支持这种双重抗 HER2 方案作为该患者群体的替代一线治疗选择。ClinicalTrials.gov NCT03863223.© 作者（或其雇主）2019。CC BY-NC 允许重复使用。不得商业再利用。请参阅权利和权限。英国医学杂志出版。

To assess the efficacy and safety of pyrotinib (an irreversible pan-HER (human epidermal growth factor receptor) inhibitor), trastuzumab, and docetaxel compared with placebo, trastuzumab, and docetaxel for untreated HER2 positive metastatic breast cancer.Randomised, double blind, placebo controlled, multicentre, phase 3 trial.40 centres in China between 6 May 2019 and 17 January 2022.590 female patients (median age 52 (interquartile range 46-58) years) with untreated HER2 positive metastatic breast cancer.Eligible patients were randomised 1:1 to receive either oral pyrotinib (400 mg once daily) or placebo, both combined with intravenous trastuzumab (8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m2) on day 1 of each 21 day cycle. Randomisation was stratified by treatment history of trastuzumab in the (neo)adjuvant setting and hormone receptor status. Patients, investigators, and the sponsor's study team were masked to treatment assignment.The primary endpoint was progression-free survival as assessed by the investigator.Of the 590 randomised patients, 297 received pyrotinib, trastuzumab, and docetaxel treatment (pyrotinib group), and 293 received placebo, trastuzumab, and docetaxel treatment (placebo group). At data cut-off on 25 May 2022, the median follow-up was 15.5 months. The median progression-free survival according to the investigator was significantly longer in the pyrotinib group than in the placebo group (24.3 (95% confidence interval 19.1 to 33.0) months versus 10.4 (9.3 to 12.3) months; hazard ratio 0.41 (95% confidence interval 0.32 to 0.53); one sided P<0.001). Treatment related adverse events of grade 3 or higher were reported in 267 (90%) of the 297 patients in the pyrotinib group and 224 (76%) of the 293 patients in the placebo group. No treatment related deaths occurred in the pyrotinib group, and one (<1%; diabetic hyperosmolar coma) treatment related death occurred in the placebo group. Survival and toxicities are still under assessment with longer follow-up.Pyrotinib, trastuzumab, and docetaxel showed superiority by significantly improving progression-free survival compared with placebo, trastuzumab, and docetaxel in patients with untreated HER2 positive metastatic breast cancer. The toxicity was manageable. The findings support this dual anti-HER2 regimen as an alternative first line treatment option in this patient population.ClinicalTrials.gov NCT03863223.© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.