Pyrotinib Combo Sustains Survival Benefits in HER2+ Breast Cancer Trial

"The long-term analysis confirms that the previously observed improvements in OS and PFS with [pyrotinib plus trastuzumab/docetaxel] compared to [trastuzumab/docetaxel] in the first-line treatment of HER2-positive metastatic breast cancer were maintained," according to the study authors.

Combining the pan-ErbB inhibitor pyrotinib (Irene) with trastuzumab (Herceptin) and docetaxel showed long-term improvements in overall survival (OS) and progression-free survival (PFS) vs placebo plus trastuzumab/docetaxel among patients with HER2-positive metastatic breast cancer, according to findings from the phase 3 PHILA trial (NCT03863223) highlighted in a poster presentation at the 2025 San Antonio Breast Cancer Symposium (SABCS).1

Data showed that the median OS was not reached (NR) in both study arms, although outcomes favored the pyrotinib arm (HR, 0.74; 95% CI, 0.56-0.98; P = .0188). In the pyrotinib and placebo arms, respectively, the OS rates were 96.6% vs 94.5% at 1 year, 88.7% vs 84.1% at 2 years, 79.6% vs 72.1% at 3 years, 72.9% vs 63.5% at 4 years, and 65.7% vs 58.5% at 5 years.

The pyrotinib combination improved PFS vs placebo plus trastuzumab/docetaxel (HR, 0.44; 95% CI, 0.36-0.54; P <.0001). In each respective arm, the 1-year PFS rates were 74.3% vs 47.0%, the 2-year rates were 47.6% vs 20.3%, the 3-year rates were 40.4% vs 9.7%, the 4-year rates were 31.9% vs 7.6%, and the 5-year rates were 29.2% vs 4.3%. Among patients with prior neoadjuvant or adjuvant therapy, the median PFS was 62.8 months (95% CI, 19.2-NR) in the experimental arm vs 10.4 months (95% CI, 6.4-13.2) in the placebo arm.

“The long-term analysis confirms that the previously observed improvements in OS and PFS with [pyrotinib plus trastuzumab/docetaxel] compared to [trastuzumab/docetaxel] in the first-line treatment of HER2-positive metastatic breast cancer were maintained,” lead study author Binghe Xu, from the Department of Medical Oncology at Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, wrote with coauthors in the poster.1 “It reinforces [a] dual anti-HER2 regimen (pyrotinib plus trastuzumab) as an established therapeutic strategy for this patient population.”

In the double-blind phase 3 PHILA study, 590 patients with HER2-positive recurrent or metastatic breast cancer were assigned 1:1 to receive pyrotinib at 400 mg orally once daily (n = 297) or matched placebo (n = 293) in combination with trastuzumab and docetaxel. Investigators administered trastuzumab at 8 mg/kg in cycle 1 and at 6 mg/kg in subsequent cycles every 3 weeks intravenously plus docetaxel at 75 mg/m2 every 3 weeks intravenously.

The trial’s primary end point was PFS per investigator evaluation. Secondary end points included OS, objective response rate, duration of response, clinical benefit rate, and adverse effects (AEs).2

Patients with no prior treatment for metastatic disease, 1 or more measurable lesions, and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Having adequate organ function was another requirement for study entry.

The median follow-up was 46.5 months (IQR, 36-55) for patients in the pyrotinib arm and 44.6 months (IQR, 31-53) for those in the placebo arm. Additionally, 25.3% and 6.5% of patients in each respective arm were still on treatment at the time of analysis.

Among those with brain metastases, the median time to onset was 16.6 months (IQR, 13-28) in the pyrotinib arm vs 9.1 months (IQR, 8-14) in the placebo arm.

With a safety data cutoff of April 30, 2024, the most common AEs in the pyrotinib and placebo arms, respectively, included diarrhea (98.7% vs 53.9%), decreased white blood cell counts (84.5% vs 85.3%), anemia (79.5% vs 48.5%), decreased neutrophil counts (79.5% vs 84.0%), vomiting (63.3% vs 15.7%), and decreased weight (60.9% vs 10.6%).

The frequency of AEs generally decreased following discontinuation of docetaxel; in the pyrotinib arm, the rate of any-grade diarrhea decreased from 98.4% to 79.9%, and the incidence of grade 3 events decreased from 46.2% to 16.1%. Of note, no grade 4 or 5 diarrhea occurred.

References

1. Xe B, Ma F, Yan M, et al. Pyrotinib or placebo in combination with trastuzumab and docetaxel for untreated HER2-positive metastatic breast cancer: long-term survival results from the phase 3 PHILA study. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract PS5-01-02.
2. A study of pyrotinib in combination with trastuzumab and docetaxel in patients with HER2 metastatic breast cancer. ClinicalTrials.gov. Updated November 23, 2023. Accessed December 19, 2025. https://tinyurl.com/443cb5w2