Efficacy of pyrotinib plus capecitabine confirmed in previously treated patients

Patients with previously treated HER2-positive metastatic breast cancer who received pyrotinib plus capecitabine had longer overall survival than patients who received lapatinib plus capecitabine, according to updated results from the phase 3 PHOEBE trial.

Patients with metastatic HER2-positive breast cancer are typically treated with the HER2-targeted therapies trastuzumab and pertuzumab in combination with a taxane, but resistance to this regimen inevitably develops. Patients who progress on this standard therapy may then be treated with lapatinib plus capecitabine or with alternative HER2-targeted therapies, such as trastuzumab plus emtansine. Pyrotinib is an irreversible tyrosine kinase receptor inhibitor that targets HER2, as well as the related proteins HER4 and HER1. A prior phase 2 clinical trial found that pyrotinib plus capecitabine led to clinical responses in previously treated patients with HER2-positive metastatic breast cancer [1]. The phase 3 PHOEBE trial (NCT03080805) compared lapatinib plus capecitabine versus pyrotinib plus capecitabine in this patient population. Prof. Binghe Xu (Chinese Academy of Medical Sciences, China) presented the results [2].

The PHOEBE trial enrolled 267 Chinese 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. Patients were randomised 1:1 to treatment with either pyrotinib plus capecitabine or lapatinib plus capecitabine. The median follow-up was 33.2 months in the pyrotinib arm and 31.8 months in the lapatinib arm. Pyrotinib plus capecitabine significantly improved median progression-free survival compared with that for lapatinib plus capecitabine: 12.5 months versus 5.6 months (HR 0.48; P<0.0001). Median overall survival was not reached for pyrotinib and was 26.9 months for lapatinib (HR 0.69; P=0.019). Two-year overall survival rates were 66.6% and 58.8%, respectively. The benefit of pyrotinib plus capecitabine was observed in most clinically relevant predefined subgroups (including metastatic disease, trastuzumab resistance, pathological grading, visceral lesions, ECOG performance status, oestrogen and progesterone receptor status, and previous lines of chemotherapy).

“In conclusion, these updated results from PHOEBE reaffirm pyrotinib plus capecitabine as an established treatment option in this population,” said Dr Xu.

1. Ma F, et al. J Clin Oncol. 2019;37:2610–2619.
2. Xu B, et al. Updated overall survival (OS) results from the phase 3 PHOEBE trial of pyrotinib versus lapatinib in combination with capecitabine in patients with HER2-positive metastatic breast cancer. GS3-02, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January 2022