Pyrotinib and Capecitabine Combo Improved PFS Compared to Lapatinib Plus Capecitabine for HER2-Positive Breast Cancer

Pyrotinib plus capecitabine to treat patients with HER2-positive metastatic breast cancer saw a statistically significant improvement in progression-free survival.

The combination of pyrotinib plus capecitabine resulted in a statistically significant improvement in progression-free survival compared with lapatinib (Tykerb) plus capecitabine as treatment of patients with previously treated HER2-positive metastatic breast cancer, according to data published in The Lancet Oncology.

The pyrotinib-plus-capecitabine combination also maintained a tolerable safety profile, presenting itself as an alternative treatment option for this cohort of patients after trastuzumab (Herceptin) and chemotherapy.

“The findings from this study suggest that pyrotinib plus capecitabine is a novel treatment for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy, and is an alternative option to the current treatment landscape, particularly in regions with scarce access to HER2-directed drugs,” wrote the investigators.

A total of 267 patients were enrolled in the phase 3 PHOEBE trial (NCT03080805), with 134 patients randomly assigned to receive pyrotinib plus capecitabine and 132 patients to lapatinib plus capecitabine.

The data interim analysis was cutoff on March 31, 2019, with a median progression-free survival of 12.5 months (95% CI, 9.7-not reached) with pyrotinib plus capecitabine compared with 6.8 months (95% CI, 5.4-8.1) with lapatinib plus capecitabine (HR, 0.39; 95% CI, 0.27-0.56; one-sided P < .0001).

Examining the safety profile, diarrhea (31% with pyrotinib vs 8% with lapatinib) and hand-foot syndrome (16% vs 15%, respectively) were the most common grade 3 or worse adverse events (AEs). More, 10% of patients in the pyrotinib group and 8% of patients in the lapatinib group reported serious AEs.

When looking at the total patient population, only 1 sudden death was considered treatment-related and reported in the lapatinib group versus none in the pyrotinib group.

“Based on the data from this study, on July 9, 2020, China National Medical Products Administration granted regular approval of pyrotinib in combination with capecitabine as second-line standard-of-care treatment for HER2-positive metastatic breast cancer,” wrote the investigators. “In addition, our findings also have wider implications for other regions of the world where access to HER2-directed agents is scarce.”

The trial was conducted across 29 hospitals in China, with patients ranging in age from 18 to 70 years and having an ECOG performance status of 0 or 1. The primary end point of progression-free survival was recorded by masked independent central review.

The first limitation of the research was the immature overall survival data. More, centralization was not possible with the data regarding HER2 status due to the involvement of 29 hospitals in China.

“Overall, pyrotinib plus capecitabine led to a statistically and clinically significant improvement in progression-free survival compared with that for lapatinib plus capecitabine in women with HER2-positive metastatic breast cancer after treatment with trastuzumab and taxanes, and has a manageable safety profile,” wrote the investigators.


Xu B, Yan M, Ma F, et al. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol 2021;22(3):351-360. doi:10.1016/S1470-2045(20)30702-6