Study details
PHOEBE included 267 patients with HER2-positive metastatic breast cancer. They had previously received trastuzumab and taxanes, and/or anthracyclines, with up to two prior lines of chemotherapy for metastatic disease.
The patients’ median age was 50 years, 79% had visceral metastases at screening, and about 26% had trastuzumab resistance, Dr. Xu said. Resistance was defined as relapse within 6 months after adjuvant treatment or progression within 3 months of treatment for metastatic disease.
A statistically significant and clinically meaningful improvement was seen in PFS, the primary endpoint of the study, Dr. Xu said.
Median PFS by blinded independent central review was 12.5 months for the pyrotinib-capecitabine combination, compared with 6.8 months for lapatinib-capecitabine (hazard ratio, 0.39; 95% confidence interval, 0.27-0.56; P < .0001).
The PFS benefit was consistently observed across all predefined subgroups, including by trastuzumab resistance.
In trastuzumab-resistant patients, the median PFS was 12.5 months for the pyrotinib combination and 6.9 months for the lapatinib combination (HR, 0.60; 95% CI, 0.29-1.21). In patients without trastuzumab resistance, the median PFS was 12.5 months and 5.6 months, respectively (HR, 0.33; 95% CI, 0.21-0.51).
Although overall survival (OS) data were not yet mature, there was a “strong trend” toward a benefit with pyrotinib, Dr. Xu said. The 12-month OS rate was 91.3% for the pyrotinib combination and 77.4% for lapatinib. The median OS was not reached in either arm at the time of analysis.
Treatment-related adverse events of grade 3 or greater occurred in 57.5% of the pyrotinib arm and 34.1% of the lapatinib arm.
Diarrhea was the most common grade 3 or greater treatment-related adverse event, occurring in 30.6% of patients in the pyrotinib arm and 8.3% of those in the lapatinib arm. No grade 4 or 5 diarrhea was seen.
Overall, diarrhea occurred in 94.8% of patients in the pyrotinib arm and 62.1% of those in the lapatinib arm. However, pyrotinib-associated diarrhea was generally of low severity, occurred early, had a short duration, was reversible, and did not lead to treatment termination, according to Dr. Xu.
This study was funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Xu reported additional disclosures related to AstraZeneca, Eisai, Pfizer, and Roche. Dr. Prat disclosed relationships with Amgen, Daiichi Sankyo, Lilly, MSD Oncology, and other companies.
SOURCE: Xu B et al. ASCO 2020, Abstract 1003