Experimental Drug Plus Chemo Boosts Survival in HER2-Positive Metastatic Breast Cancer

Treatment with the investigational therapy pyrotinib plus the chemotherapy capecitabine induced longer survival outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, compared with the combination of Tykerb (lapatinib) and capecitabine, according to study results.

“Patients with metastatic HER2-positive breast cancer are typically treated with the HER2-targeted therapies trastuzumab (Herceptin) and pertuzumab (Perjeta) in combination with a taxane, but resistance to this regimen inevitably develops,” Dr. Binghe Xu, a professor in the Department of Medical Oncology at Peking Union Medical College in China, said in a news release announcing the data.

Traditionally, patients whose disease progresses after receiving this therapy are then often treated with Tykerb plus capecitabine or other HER2-targeted therapies. The problem, according to Xu, is that many of those treatments don’t hold their effects for long and a patient’s disease may become resistant to therapy.

As a result, Xu and colleagues began assessing the efficacy of the experimental drug pyrotinib — an irreversible tyrosine kinase inhibitor (TKI) that targets the HER2 protein — in combination with capecitabine in the PHOEBE trial. Of note, an irreversible therapeutic blocks certain enzymes that cancer cells need to grow and may ultimately kill cancer cells.

At the 2021 San Antonio Breast Cancer Symposium, Xu and colleagues presented data from an updated analysis of the phase 3 trial.

The researchers randomly assigned 134 patients to receive 400 milligrams (mg) of pyrotinib plus capecitabine at 1,000 mg/m2 and 132 patients to receive 1,250 mg of lapatinib plus the same dosage of capecitabine the other group received.

Assessing progression-free survival (the time a patient survives before their disease progresses) was the main goal of the study. Some of the other goals included analyzing the safety of the study drug, as well as measuring overall survival, objective response rates (proportion of patients whose disease partially or completely responds to treatment) and duration of response. Patients remained on treatment until disease progression, unacceptable toxicity, death, consent withdrawal, investigator decision or completion.

The study results demonstrated that at an average follow-up of 33.2 months, a median overall survival was not yet reached in the group that received pyrotinib. However, a median overall survival of 26.9 months was reached in the Tykerb group.

The estimated 24-month overall survival rate was 66.6% in the pyrotinib group and 58.8% in the Tykerb group. Moreover, 121 patients in the Tykerb group had disease progression or died, compared with 99 patients who received pyrotinib.

The use of pyrotinib plus capecitabine was also associated with a significant improvement in progression-free survival compared with the Tykerb combination (12.5 months vs. 5.6 months).

A little more than half of the patients (58.2%) in the pyrotinib group required post-discontinuation therapy compared with 74.2% of patients in the Tykerb group. The most common therapy given was Herceptin (trastuzumab) in 44.8% of the pyrotinib group and 49.2% in the Tykerb group. At the time of this updated analysis, 40.3% of patients in the pyrotinib group and 52.3% of the Tykerb group had died.

The results of this trial, according to Xu, have led to the approval of pyrotinib plus capecitabine as a standard-of-care treatment option in the second-line setting for patients with HER2-positive metastatic breast cancer in China.

“Among the patients enrolled in the study, pyrotinib plus capecitabine had a manageable safety profile and led to a statistically and clinically significant improvement in progression-free and overall survival compared with that for lapatinib,” Xu said in the release. “The updated analysis of overall survival we present here reaffirms pyrotinib plus capecitabine as a viable treatment option in this patient population.”

A version of this article was originally published on Targeted Oncology as, “Updated Analysis Shows Improved OS for Pyrotinib Over Lapatinib in HER2-Positive Breast Cancer.”

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