Pyrotinib Associated With Overall Survival Benefit for Certain Patients With Breast Cancer

Pyrotinib plus capecitabine demonstrated overall survival (OS) benefits compared to lapatinib plus capecitabine in patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, 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 progress on this standard therapy may then be treated with the HER2-targeted tyrosine kinase inhibitor (TKI) lapatinib in combination with the chemotherapeutic capecitabine, according to the investigators. However, lapatinib, as well as many other available HER2-targeted TKIs, are reversible and do not sustain the inhibition of HER2 signaling. This could lead to the development of treatment resistance.

“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), also known as HER1. Prior research has found that pyrotinib plus capecitabine led to clinical responses in previously treated patients with HER2-positive metastatic breast cancer. In the phase 3 PHOEBE trial, investigators sought to understand the impact of pyrotinib compared with that of lapatinib in this patient population.

To conduct the study, 267 patients were enrolled 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. Participants were randomly assigned to receive either pyrotinib plus capecitabine or lapatinib plus capecitabine.

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, compared with an OS of 26.9 months in the lapatinib arm.

Further, progression-free survival was significantly longer in the pyrotinib arm, at 12.5 months for patients receiving the drug 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]. SABCS; December 7, 2021. Accessed December 14, 2021. https://aacr.ent.box.com/s/j27o8oos08va5i68ifiewodannb8iyov