Pyrotinib, Capecitabine Combination Therapy Improves Clinical Outcomes for Certain Patients with HER2-Positive Breast Cancer

Pyrotinib, in combination with capecitabine, improved overall survival (OS) in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer compared to lapatinib plus capecitabine, according to updated results from the phase 3 PHOEBE trial presented at the San Antonio Breast Cancer Symposium.

“Patients with metastatic HER2-positive breast cancer are typically treated with the HER2-targeted therapies trastuzumab (Herceptin) and pertuzumab (Perjeta) in combination with a taxane, but resistance to this regimen inevitably develops,” said Binghe Xu, MD, PhD, professor of medical oncology at the Chinese Academy of Medical Sciences, in a press release.

Patients who develop resistance to the standard trastuzumab and pertuzumab therapy and experience disease progression are then treated with the HER2-targeted tyrosine kinase inhibitor (TKI) lapatinib in combination with the chemotherapeutic capecitabine or with alternative HER2-targeted therapies, such as trastuzumab emtansine. However, multiple HER2-targeted TKIs—including lapatinib—are reversible, and inhibition of HER2 signaling is not maintained.

“There is an urgent unmet need for additional HER2-targeted therapies for patients who progress on standard therapies in countries and regions where access to HER2-directed agents is scarce,” Xu said in the release.

Pyrotinib is an irreversible TKI that targets HER2, as well as the related proteins HER4 and epidermal growth factor receptor (EGFR). A previous phase 2 trial found that the combination therapy of pyrotinib plus capecitabine was associated with clinical responses in previously treated patients with HER2-positive metastatic breast cancer.

The phase 3 PHOEBE trial, designed to examine the impact of pyrotinib compared to lapatinib, enrolled 267 patients with HER2-positive metastatic breast cancer who had been previously treated with trastuzumab and taxanes, and up to 2 previous lines of chemotherapy in the metastatic setting. The median follow-up was 33.2 months in the pyrotinib arm and 31.8 months in the lapatinib arm. At the time of data cutoff, 40.3% of patients in the pyrotinib arm and 52.3% in the lapatinib arm had died.

According to the investigators, patients treated with pyrotinib plus capecitabine had a 31% lower risk of death than those treated with lapatinib and capecitabine. OS was not reached in the pyrotinib arm, whereas the OS in the lapatinib arm was 26.9 months.

Further, progression-free survival was significantly longer in the pyrotinib arm at 12.5 months compared to 5.6 months in the lapatinib arm. Disease progression risk was 52% lower in the pyrotinib arm.

“Among the patients enrolled in the study, pyrotinib plus capecitabine had a manageable safety profile and led to a statistically and clinically significant improvement in progression-free and overall survival compared with that for lapatinib,” Xu said in the release. “The updated analysis of overall survival we present here reaffirms pyrotinib plus capecitabine as a viable treatment option in this patient population.”

REFERENCE

Investigational therapy pyrotinib with chemotherapy may improve outcomes in patients with pretreated HER2-positive breast cancer [news release]. AACR; December 7, 2021. Accessed December 1, 2021.