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.

Methods

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

多中心、双盲、随机、安慰剂对照的第3阶段试验。

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

在中国的40个中心，研究时间从2019年5月6日至2022年1月17日。

590 female patients with untreated HER2 positive metastatic breast cancer.

590名未接受治疗的HER2阳性转移性乳腺癌女性患者。

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.

符合条件的患者按1:1的比例随机分配，接受不可逆的全HER抑制剂吡咯替尼（每日口服400毫克）或安慰剂治疗，两者均与静脉注射曲妥珠单抗（首周期8毫克/公斤，随后周期6毫克/公斤）和多西他赛（每21天治疗周期的第1天75毫克/平方米）联合使用。

main_outcome_measure

The primary endpoint was investigator assessed progression-free survival.

主要终点是研究者评估的无进展生存期。

Results

590 patients were randomised and received treatment (297 in the pyrotinib group and 293 in the placebo group).

590名患者被随机分配并接受了治疗（297名在吡咯替尼组，293名在安慰剂组）。

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.

截至2024年4月30日，在吡咯替尼组中位随访时间为35.7个月，在安慰剂组中位随访时间为34.3个月时，分别有59名（20%）和87名（30%）患者死亡。

Overall survivalwas longer in the pyrotinib group (hazard ratio0.64 (95% confidence interval(CI) 0.46 to 0.89); nominal one-sided P=0.004).

在吡咯替尼组中，总生存期更长（风险比为0.64（95%置信区间（CI）0.46至0.89）；名义单侧P=0.004）。

At end of follow-up, neither group had reached the median overall survival. Improvement in progression-free survivalin 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 ratio0.44 (95% CI 0.36 to 0.53); nominal one sided P<0.001).

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% CI 19.3至27.8）对比10.5个月（9.5至12.4），风险比为0.44（95% CI 0.36至0.53）；名义单侧P<0.001）。

Adverse eventprofiles remained consistent with the interim analysis for type, frequency, and severity.

不良事件的特征与中期分析保持一致，包括类型、频率和严重程度。

After discontinuation of docetaxel, the overall incidenceof adverse events decreased substantially.

停用多西他赛后，不良事件的总体发生率显著下降。

As of 30 May 2025, with a median follow-up of 45.5 months, the pyrotinib based regimen showed consistent and prolonged survival benefit.

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一致且持久的生存益处。

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 survivaland improving overall survivalfor initial treatment of HER2 positive metastatic breast cancer.

第三阶段PHILA试验的最新分析证实，与安慰剂相比，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HER2阳性转移性乳腺癌初始治疗的总生存方面具有优越性。

The safety profile remained consistent with interim findings, with no new safety signals identified during extended follow-up.

安全性特征与中期发现保持一致，延长随访期间未发现新的安全信号。

This analysis reinforces the efficacy of this dual anti-HER2 (pyrotinib plus trastuzumab) regimen as an effective treatment strategy for this patient population.

这项分析加强了这种双靶向HER2（吡咯替尼加曲妥珠单抗）方案作为这一患者群体有效治疗策略的疗效。

trial_registration

ClinicalTrials.gov NCT03863223.

ClinicalTrials.gov NCT03863223。