近日，中国医学科学院北京协和医学院徐兵河团队研究了吡咯替尼或安慰剂联合曲妥珠单抗和多西他赛治疗HER2阳性转移性乳腺癌症的疗效与安全性。相关论文于2026年3月16日发表在《英国医学杂志》上。

为了报告PHILA 3期试验的最新结果，研究组评估了吡咯替尼或安慰剂联合曲妥珠单抗和多西他赛在未经治的人表皮生长因子受体2（HER2）阳性转移性乳腺癌患者中的疗效和安全性。2019年5月6日至2022年1月17日，研究组在中国40个中心进行了一项多中心、双盲、随机、安慰剂对照的3期试验，共招募了590名未经治的HER2阳性转移性乳腺癌女性患者。

研究组将符合条件的患者按1:1的比例随机分配，接受不可逆的泛HER抑制剂吡咯替尼（400毫克口服，每日一次）或安慰剂治疗，两者均在每个21天治疗周期的第一天与静脉注射曲妥珠单抗（第一个周期8毫克/公斤体重，后续周期6毫克/公斤体重）和多西他赛（75毫克/平方米体表面积）联合使用。主要终点是研究者评估的无进展生存期。

590名患者被随机分组并接受了治疗（吡咯替尼组297人，安慰剂组293人）。截至2024年4月30日，吡咯替尼组中位随访时间为35.7个月，安慰剂组为34.3个月，期间分别有59名（20%）和87名（30%）患者死亡。吡咯替尼组的总生存期更长（风险比0.64（95%置信区间0.46至0.89）；名义单侧P=0.004）。随访结束时，两组均未达到中位总生存期。吡咯替尼组的无进展生存期改善得以维持（22.1个月（95%置信区间19.3至27.8）对比10.5个月（9.5至12.4），风险比0.44（95%置信区间0.36至0.53）；名义单侧P<0.001）。不良事件特征在类型、频率和严重程度上与中期分析结果保持一致。停用多西他赛后，不良事件的总体发生率显著下降。截至2025年5月30日，中位随访时间为45.5个月，基于吡咯替尼的方案显示出持续且延长的生存获益。

该研究的更新分析证实，对于HER2阳性转移性乳腺癌的初始治疗，吡咯替尼联合曲妥珠单抗和多西他赛在维持更长的无进展生存期和改善总生存期方面优于安慰剂联合曲妥珠单抗和多西他赛。安全性特征与中期结果一致，延长随访期间未发现新的安全信号。该分析进一步证实了这种双重抗HER2（吡咯替尼联合曲妥珠单抗）方案作为该类患者人群有效治疗策略的疗效。

附：英文原文

Title: Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2 positive metastatic breast cancer: long term survival results from randomised phase 3 PHILA trial

Author: Fei Ma, Min Yan, Wei Li, Quchang Ouyang, Zhongsheng Tong, Yuee Teng, Yongsheng Wang, Shusen Wang, Cuizhi Geng, Ting Luo, Jincai Zhong, Qingyuan Zhang, Qiang Liu, Xiaohua Zeng, Tao Sun, Qinguo Mo, Shoubing Zhou, Peidong Li, Jing Cheng, Xiaojia Wang, Jianyun Nie, Jin Yang, Xinhong Wu, Xinshuai Wang, Huiping Li, Guangyu Yao, Yang Fan, Jiaman Lin, Xiaoyu Zhu, Binghe Xu

Issue&Volume: 2026/03/16

Abstract:

Objective To report updated results of the phase 3 PHILA trial, which evaluated the efficacy and safety of pyrotinib or placebo in combination with trastuzumab and docetaxel in patients with untreated human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer.

Design Multicentre, double blind, randomised, placebo controlled phase 3 trial.

Setting 40 centres in China, 6 May 2019 to 17 January 2022.

Participants 590 female patients with untreated HER2 positive metastatic breast cancer.

Interventions Eligible patients were randomly assigned in a 1:1 ratio to receive either the irreversible pan-HER inhibitor pyrotinib (400 mg orally once daily) or placebo, both in combination with intravenous trastuzumab (8 mg/kg for the first cycle, then 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m2) on day 1 of each 21 day treatment cycle.

Main outcome measure The primary endpoint was investigator assessed progression-free survival.

Results 590 patients were randomised and received treatment (297 in the pyrotinib group and 293 in the placebo group). As of 30 April 2024, during a median follow-up of 35.7 months in the pyrotinib group and 34.3 months in the placebo group, 59 (20%) and 87 (30%) patients died, respectively. Overall survival was longer in the pyrotinib group (hazard ratio 0.64 (95% confidence interval (CI) 0.46 to 0.89); nominal one-sided P=0.004). At end of follow-up, neither group had reached the median overall survival. Improvement in progression-free survival in the pyrotinib group was maintained (22.1 months (95% CI 19.3 to 27.8) v 10.5 months (9.5 to 12.4), hazard ratio 0.44 (95% CI 0.36 to 0.53); nominal one sided P<0.001). Adverse event profiles remained consistent with the interim analysis for type, frequency, and severity. After discontinuation of docetaxel, the overall incidence of adverse events decreased substantially. As of 30 May 2025, with a median follow-up of 45.5 months, the pyrotinib based regimen showed consistent and prolonged survival benefit.

Conclusions The updated analysis of the phase 3 PHILA trial confirmed the superiority of pyrotinib in combination with trastuzumab and docetaxel over placebo in combination with trastuzumab and docetaxel in sustaining longer progression-free survival and improving overall survival for initial treatment of HER2 positive metastatic breast cancer. The safety profile remained consistent with interim findings, with no new safety signals identified during extended follow-up. This analysis reinforces the efficacy of this dual anti-HER2 (pyrotinib plus trastuzumab) regimen as an effective treatment strategy for this patient population.

DOI: 10.1136/bmj-2025-087259

Source: https://www.bmj.com/content/392/bmj-2025-087259