Abstract
A Chinese study of patients with HER2-positive metastatic breast cancer shows that the HER2 inhibitor pyrotinib increases progression-free survival and objective response rates over lapatinib. Pyrotinib did increase the incidence of side effects such as diarrhea and hand–foot syndrome. However, about 54% of trial participants had previously taken trastuzumab, so the study's results may not hold true in the United States, where most patients receive it.
A phase II study shows that the tyrosine kinase inhibitor pyrotinib (Jiangsu Hengrui Medicine) outperforms lapatinib (Tykerb; Novartis) in women with HER2-positive metastatic or relapsed breast cancer. The drug has been greenlighted for these patients in China, but researchers say the findings may not be generalizable to patients in the United States.
Patients in the United States with metastatic, HER2-positive breast cancer usually receive docetaxel plus the HER2-blocking antibodies trastuzumab (Herceptin; Genentech) and pertuzumab (Perjeta; Genentech). The combination of lapatinib, which inhibits HER2, and capecitabine (Xeloda; Genentech) is an option for those whose disease progresses after treatment with trastuzumab and pertuzumab.
A newer HER2 inhibitor, pyrotinib is under investigation to treat a variety of cancers. In 2017, a phase I study suggested that the drug was well tolerated and might benefit patients with HER2-positive metastatic breast cancer.
To test the drug's effectiveness against this malignancy, researchers at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing and other institutions randomly assigned 128 women to receive capecitabine and either pyrotinib or lapatinib. All of them had previously received taxanes and anthracyclines, and 53.9% had received trastuzumab.
The most common side effect of any grade in the pyrotinib group was diarrhea, which affected 96.9% of patients, versus 44.4% in the lapatinib group. Severe side effects were more common in patients who received pyrotinib, with 61.3% of patients suffering grade 3 or 4 adverse events, compared with 47.6% of those in the lapatinib group. The most common side effect of at least grade 3 was hand–foot syndrome, which affected 24.6% of patients in the pyrotinib group and 20.6% in the lapatinib group.
Data on effectiveness gave pyrotinib the advantage. The objective response rate in patients who received pyrotinib was 78.5%, versus 57.1% for those who received lapatinib. Median progression-free survival (PFS) for the pyrotinib group was 18.1 months, compared with 7 months for the lapatinib group. The researchers found that PFS was longer for pyrotinib regardless of whether patients had previously received trastuzumab. The authors have already begun a phase III study of patients with metastatic breast cancer who will receive docetaxel plus trastuzumab with or without pyrotinib.
“The study, quite unequivocally, confirms the comparative effectiveness of pyrotinib over lapatinib in producing objective responses,” says Aju Mathew, MD, of the University of Kentucky College of Medicine in Lexington, who wasn't connected to the research. That the drug is moving on to phase III testing in China “holds great promise for the region where nearly one third of the world's population resides.”
However, questions remain about whether the drug will be relevant to other populations, says Sandra Swain, MD, of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC. Almost all patients with metastatic breast cancer in the United States would receive trastuzumab and pertuzumab, but only about 30% of patients in the study had been treated with an anti-HER2 antibody in the metastatic setting. This relatively small number means the study can't resolve whether pyrotinib is effective in patients who have progressed on anti-HER2 therapy, Swain says. –Mitch Leslie
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