Pyrotinib-Based Dual Anti-HER2 Regimen Extended Survival in Metastatic Breast Cancer

By: Mary Ellen Schneider

From: cancertherapyadvisor.com

Pyrotinib plus trastuzumab and docetaxel outperformed trastuzumab and docetaxel alone as an initial treatment for HER2-positive metastatic breast cancer, according to findings published in the BMJ.

The final analysis of the phase 3 PHILA taril (NCT03863223) demonstrated significant improvements in both progression-free survival (PFS) and overall survival (OS).

“Pyrotinib, a small molecule, irreversible, pan-HER receptor tyrosine kinase inhibitor, has shown promising antitumour activity in both single agent and combination treatment settings,” the researchers wrote. “By targeting not only HER2 but also epidermal growth factor (EGFR/HER1) and HER4, pyrotinib offers a unique mechanism of action that may lead to sustained inhibition of HER signalling and enhanced antitumour effects compared with reversible HER2 targeted tyrosine kinase inhibitors.”

The PHILA trial compares pyrotinib plus trastuzumab and docetaxel versus placebo plus trastuzumab and docetaxel among adults with treatment-naïve HER2-positive recurrent or metastatic breast cancer. A total of 590 patients were randomly assigned to 400 mg oral pyrotinib daily or placebo. Both groups received intravenous trastuzumab (8 mg/kg in cycle 1 and 6 mg/kg subsequently) and docetaxel on day 1 of each 21-day treatment cycle.

In a previously reported interim analysis, the pyrotinib-based regimen was associated with a median PFS of 24.3 months compared with 10.4 months for the placebo-based regimen. In this final analysis, the researchers assessed PFS 2 years after the interim analysis cutoff date. As of April 30, 2024, the PFS benefit was sustained in the pyrotinib arm (22.1 vs 10.5 months; hazard ratio [HR], 0.44; 95% CI, 0.36-0.53; P <.001).

At the long-term analysis cutoff of May 30, 2025, the PFS benefit for the pyrotinib regimen remained “consistent and prolonged.” At 5 years, the PFS rates were 29% in the pyrotinib arm and 4% in the placebo arm.

The pyrotinib arm also showed a significant OS benefit by April 30, 2025, compared with the placebo arm (HR, 0.64; 95% CI 0.46-0.89; P =.004). Median OS was not reached in either arm. The 5-year OS rates were 66% in the pyrotinib arm and 58.5% in the placebo arm.

Grade 3 or higher treatment-related adverse events occurred in 91% of patients in the pyrotinib arm and 77% of patients in the placebo arm. Patients in the pyrotinib arm were more likely to experience grade 3 decreased white blood cell count (53% vs 51%) and grade 3 diarrhea (48% vs 4%). Diarrhea occurred mostly in the initial cycle of treatment, and researchers wrote that loperamide hydrochloride and dose modifications controlled the condition.

The incidence of all adverse events decreased after discontinuing docetaxel, the researchers noted.

“This updated analysis further reinforces the pyrotinib-based regimen as an efficacious strategy for the initial treatment of patients with HER2-positive metastatic breast cancer,” the researchers wrote.