- Pyrotinib+capecitabine compared with lapatinib+capecitabine confers a statistically significant improvement in PFS after trastuzumab and chemotherapy in patients with HER2-positive metastatic breast cancer (MBC).
Why this matters
- Multiple HER2-directed treatments are available for HER2-positive MBC, but because of drug resistance, alternative treatments are required.
- The irreversible pan-HER inhibitor pyrotinib combined with capecitabine showed clinically meaningful benefits in phase 1 and 2 trials.
- Pyrotinib was approved as a second-line standard of care for HER2-positive MBC in China.
- The phase 3 PHOEBE trial enrolled 267 patients with HER2+ MBC treated with trastuzumab and taxanes and/or anthracyclines; up to 2 prior lines of chemotherapy for metastatic disease were allowed.
- Patients were randomly assigned (1:1; stratification by hormone receptor status and prior lines of chemotherapy) to receive pyrotinib or lapatinib plus capecitabine.
- Primary endpoint: PFS (blinded independent central review).
- This is a planned interim analysis.
- Funding: Jiangsu Hengrui Medicine.
- Median PFS:
- 12.5 months (95% CI, 9.7-not reached) with pyrotinib+capecitabine vs
- 6.8 months (95% CI, 5.4-8.1 months) with lapatinib+capecitabine.
- The HR (0.39, 95% CI, 0.27-0.56) met the criterion for statistical significance.
- Prolonged PFS with pyrotinib+capecitabine was also observed in patients with trastuzumab-resistant disease.
- OS data were not mature, but the trend favored pyrotinib+capecitabine.
- The most common grade ≥3 treatment-related adverse events were diarrhea (30.6% with pyrotinib+capecitabine and 8.3% with lapatinib+capecitabine) and hand-foot syndrome (16.4% and 15.2%, respectively).
“Pyrotinib is a new pan-HER inhibitor with clinical value across two phase 3 clinical trials [Ed. note: PHOEBE and PHENIX]," says Aleix Prat, head of the Medical Oncology Department of the Hospital Clinic, Barcelona, Spain. "However, its value in the setting of pertuzumab, T-DM1, tucatinib, DS8201a, and neratinib is less clear ... the toxicity profile needs attention.”