Pyrotinib plus capecitabine showed superior clinical benefit over lapatinib plus capecitabine in previously treated patients with HER-2 positive metastatic breast cancer, according to the results of an open-label, multicenter, randomized phase II clinical trial recently published in the Journal of Clinical Oncology.
The clinical trial enrolled 128 Chinese patients between May 29, 2015, and March 15, 2016, who had HER2-positive relapsed or metastatic breast cancer that had been treated with prior taxanes, anthracyclines, and/or trastuzumab. Patients were randomly assigned treatment with pyrotinib in combination with capecitabine (n=65) or lapatinib in combination with capecitabine (n=63).
Pyrotinib is an oral, irreversible pan-HER receptor tyrosine kinase inhibitor, and lapatinib is an oral HER2 tyrosine kinase inhibitor currently approved by the US Food and Drug Administration in combination with capecitabine for metastatic breast cancer.
The study population had a median age of 48 years (range: 25 to 70 years), and most patients had visceral disease (76.6%). Overall 62.5% of patients were hormone receptor positive, and approximately half of patients (53.9%) had previously received trastuzumab, whether it be in the (neo)adjuvant and/or metastatic settings. Patients in the pyrotinib group received a median of 20 treatment cycles (range: 2 to 30), and patients in the lapatinib group received a median of 10 treatment cycles (range: 2 to 28).
The trial met its primary endpoint, showing that the pyrotinib group had a more than 20 percentage point superior investigator-assessed overall response rate (ORR) compared with the lapatinib group (78.5% vs 57.1%); the difference was statistically significant (P=.01). In addition, the pyrotinib group had a nearly 11-month longer median progression-free survival (PFS) and 64% lower likelihood of disease progression or death compared with the lapatinib group (18.1 vs 7.0 months; HR=0.36; 95% CI, 0.23–0.58; P=.001).
As for the safety profile, more patients in the pyrotinib group than the lapatinib group reported grade 3 or 4 adverse events (61.3% vs 47.6%). The most common grade 3 events for the pyrotinib and lapatinib groups were hand-foot syndrome (24.6% vs 20.6%), diarrhea (15.4% vs 4.8%), decreased neutrophil count (9.2% vs 3.2%), and decreased white blood cell count (7.7% vs 1.6%), all of which were higher in the pyrotinib group.
A total of 6 patients (4.7%) discontinued treatment due to toxicity, with 3 from the pyrotinib group and 3 from the lapatinib group.
“To our knowledge, this is the first trial to demonstrate that a novel epidermal growth factor receptor/HER2–targeting tyrosine kinase inhibitor provides ORR and PFS benefits over lapatinib,” the study authors reported.
A phase III trial known as PHOEBE is underway to evaluate pyrotinib plus capecitabine versus lapatinib plus capecitabine in previously treated patients with HER2-positive metastatic breast cancer.