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Pyrotinib plus capecitabine improves survival in pre-treated patients with HER2+ breast cancer

The phase III PHOEBE trial demonstrated that patients with previously treated, HER2-positive metastatic breast cancer who received pyrotinib plus capecitabine had a longer overall survival than patients who received lapatinib plus capecitabine. These results can be of utmost importance for patients who progress on standard therapies in countries and regions where access to HER2-directed agents such as trastuzumab emtansine is scarce.

To date, many international guidelines recommend the use of trastuzumab emtansine (T-DM1) as a second-line therapy for patients with HER2-positive (HER2+) breast cancer after progression on trastuzumab. However, T-DM1 is not approved for metastatic disease in many countries in South America, Eastern Europe and Asia, and novel treatment options are therefore needed. Pyrotinib is a small-molecular, irreversible, pan-ErbB receptor tyrosine kinase inhibitor targeting EGFR, HER2 and HER4. In the randomised phase III PHOEBE study, pyrotinib plus capecitabine previously demonstrated a clinically meaningful benefit and acceptable tolerability in patients with HER2+ metastatic breast cancer (mBC) who were previously treated with taxanes, anthracyclines and/or trastuzumab. At the interim analysis, progression-free survival (PFS) improved from 6.8 months in the lapatinib + capecitabine arm to 12.5 months in the pyrotinib + capecitabine arm (HR [95%CI]: 0.39 [0.27-0.56]; p< 0.0001). Overall survival (OS) data were not yet mature at the interim analysis. At SABCS 2021, dr. Xu presented an updated OS analysis of this study.

PHOEBE study design

The multicentre, open-label, randomised controlled, phase III PHOEBE trial enrolled 267 Chinese patients with HER2+ mBC who were previously treated with trastuzumab and taxanes and/or anthracyclines. Up to two previous lines of chemotherapy in the metastatic setting were allowed. All patients were required to have at least one measurable lesion and an ECOG performance status of 0 or 1. Patients were randomly assigned (1:1) to receive either pyrotinib (400 mg, orally, once a day) plus capecitabine (1,000 mg/m2, orally, twice daily on days 1-14 of each 21-day cycle) or lapatinib (1,250 mg, orally, once a day) plus capecitabine.


As of the data cut-off for the updated OS analysis (March 2021), the median follow-up was 33.2 months in the pyrotinib arm and 31.8 months in the lapatinib arm. At that time, 40.3% of patients in the pyrotinib arm and 52.3% in the lapatinib arm had died. Patients treated with pyrotinib plus capecitabine had a 31% lower risk of death than those treated with lapatinib and capecitabine (HR [95%CI]: 0.69 [0.48-0.98]; p=0.02). Median OS was not reached in the pyrotinib arm compared with a median OS of 26.9 months in the lapatinib arm. At 24 months, OS rates in the pyrotinib and lapatinib arms were 66.6% and 58.8%, respectively. The OS benefit was consistent among all prespecified subgroups.

Furthermore, patients in the pyrotinib arm had a significantly longer PFS than those in the lapatinib arm (12.5 months versus 5.6 months), with a 52% lower risk of disease progression (HR [95%CI]: 0.48 [0.37-0.63];  p<0.0001). The PFS was in all predefined subgroups generally consistent with the overall result. Among the patients without a trastuzumab-resistant condition, the hazard ratios for OS and PFS were respectively 0.60 and 0.44, as compared to hazard ratios of 0.94 and 0.58 for trastuzumab-resistant patients. Across subgroups with different numbers of previous lines of chemotherapy (0, 1 or 2 lines), the benefits of pyrotinib as compared with lapatinib were noted for both OS and PFS.


With extended follow-up, pyrotinib plus capecitabine demonstrated a statistically significant OS improvement compared to lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer progressing on trastuzumab and chemotherapy. The benefit of pyrotinib plus capecitabine was observed in most clinically relevant subgroups in both the updated OS and PFS analysis. This updated analysis of the PHOEBE trial therefore reaffirmed pyrotinib plus capecitabine as a feasible treatment option in this patient population.


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. Presented at SABCS 2021; abstract GS3-02.

Speaker Binghe Xu

Binghe Xu

Binghe Xu, MD, PhD, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China


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