Pyrotinib regimen improves PFS in HER2-positive metastatic breast cancer
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Key takeaways:
- The addition of pyrotinib to trastuzumab and docetaxel improved 4-year OS vs. placebo for patients with HER2-positive metastatic breast cancer.
- The pyrotinib regimen also improved PFS.
SAN ANTONIO — The addition of pyrotinib to first-line trastuzumab and docetaxel improved PFS among patients with HER2-positive metastatic breast cancer, according to study results presented at San Antonio Breast Cancer Symposium.
The combination also exhibited a manageable safety profile.
“This updated analysis further reinforces [this regimen] as a well-established and efficacious therapeutic strategy for this patient population,” Binghe Xu, MD, of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, said during a presentation.
Background and methods
Approximately 15% to 20% of patients with breast cancer have HER2 mutations.
Pertuzumab (Perjeta, Genentech) in combination with trastuzumab and docetaxel is the current standard first-line treatment for this population.
The randomized phase 3 PHILA study included 590 patients (median age, 52 years) treated at 40 centers in China.
Eligible patients had histologically confirmed HER2-positive recurrent or metastatic breast cancer and had not received treatment for metastatic disease. They also had at least one measurable lesion, adequate organ function and an ECOG performance status of 0 or 1.
Researchers randomly assigned patients to 400 mg oral pyrotinib once daily (n = 297) or placebo (n = 293), in addition to IV trastuzumab (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) and docetaxel (75 mg/m2) on day 1 of each 21-day cycle.
Investigator-assessed PFS served as the primary endpoint.
A prior interim analysis showed the addition of pyrotinib (Hengrui Therapeutics) to trastuzumab and docetaxel significantly improved PFS compared with the addition of placebo.
Results showed improved investigator-assessed PFS in the pyrotinib group (median, 24.3 months vs. 10.4 months; HR = 0.41; 95% CI, 0.32-0.53). OS data remained immature at that time.
At SABCS, Xu reported data from a prespecified final PFS analysis, as well as estimated OS data and safety outcomes after 3 years of follow-up. Data cutoff occurred on April 30.
Results, next steps
Median follow-up was 35.7 months in the pyrotinib group and 34.3 months in the placebo.
Results showed improved investigator-assessed PFS with pyrotinib (median, 22.1 months vs. 10.5 months; HR = 0.44; 95% CI, 0.36-0.53). The PFS benefit appeared consistent across nearly all analyzed subgroups.
At data cutoff, fewer patients assigned pyrotinib had died (19.9% vs. 29.7%).
Estimated 4-year OS rates also favored pyrotinib (74.5% vs. 64.3%; HR = 0.64; 95% CI, 0.46-0.89).
Researchers noted no new safety signals.
Grade 3 or higher treatment-related adverse events occurred more frequently in the pyrotinib cohort (90.9% vs. 77.5%). The most common such events included decreased neutrophil count (63% vs 64.8%) and decreased white blood cell count (53.2% vs 50.9%).
A higher percentage of pyrotinib-treated patients developed treatment-related serious adverse events (27.3% vs. 7.5%). Fewer treatment-related deaths occurred in the pyrotinib group (0% vs. 0.3%).
“After an extended follow-up period, the updated analysis demonstrates that [the pyrotinib regimen] provides sustained longer PFS compared to [trastuzumab and docetaxel alone], which translates into potential longer OS ... in the first-line treatment of HER2-positive metastatic breast cancer,” Xu said.
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Xu B, et al. Abstract GS1-03. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-13, 2024; San Antonio.
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