Novel Combination Shows Survival Benefit in HER2-Positive Metastatic Breast Cancer

The combination of pyrotinib plus Xeloda (capecitabine) provides a better progression-free survival (PFS) rate than Tykerb (lapatinib) plus Xeloda in patients with HER2-positive metastatic breast cancer (mBC) who were previously treated with Herceptin (trastuzumab) and chemotherapy, according to recent data.

Although patients with HER2-positive metastatic breast cancer have several therapy options to choose from, not all are available in all regions of the world, said Dr. Binghe Xu, director of the department of medical oncology at the Cancer Hospital and Institute of the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing.

In an interview with OncLive®, CURE®’s sister publication, Xu explained that inevitable drug resistance also requires additional options, which is why researchers are investigating pyrotinib, a pan-ErbB receptor tyrosine kinase inhibitor that targets EGFR, HER2, and HER4.

Because pyrotinib plus Xeloda has shown promising efficacy and safety in patients with HER2-positive mBC in phase 1 and phase 2 studies, researchers set out to further test these attributes in the phase 3 PHOEBE trial, the data from which was presented at the 2020 ASCO Virtual Scientific Program.

"In the previous phase 2 study, we compared pyrotinib plus capecitabine versus lapatinib plus capecitabine in pretreated patients," Xu said. "The overall response rate and progression-free survival were significantly improved with pyrotinib plus capecitabine."

In the open-label, multicenter, randomized phase 3 PHOEBE trial, 267 patients were enrolled from July 2017 through October 2018, all with HER2-positive mBC. To be included, patients must have already been treated with Herceptin and taxanes and/or anthracyclines.

Patients were then randomly assigned to receive either pyrotinib 400 milligrams (mg) or Tykerb 1250 mg once daily, continuously, plus Xeloda 1000 mg/m² twice daily on days 1-14 of 21-day cycles. Measuring progression-free survival (PFS), or the time from the start of treatment until disease worsened, was the primary goal of the study.

At a median follow up of 9.9 months, the median PFS was 12.5 months in the pyrotinib plus Xeloda arm compared to 6.8 months in the Tykerb plus Xeloda arm.

The objective response rate (the proportion of complete and partial responses to treatment) was 67.2% in the pyrotinib arm and 51.5% in the Tykerb arm. Partial response was observed in 61.9% and 50.8% of patients and complete response in 5.2% and 0.8% of patients, respectively. The clinical benefit rate was 73.1% in the pyrotinib arm vs. 59.1% in the Tykerb arm.

Xu noted that while overall survival (OS) data were not yet mature at the time of the presentation, researchers found that there was a strong trend toward prolonged survival with pyrotinib plus Xeloda, with an OS rate of 91.3% vs. 77.4% in the Tykerb group.

In terms of side effects and safety, Xu noted that the safety profile of the pyrotinib/Xeloda combination was manageable. Side effects related to treatment that were severe or serious were observed in 57.5% of patients in the pyrotinib arm and 34.1% of patients in the Tykerb arm.

The most common severe or serious side effects were diarrhea (30.6% vs 8.3%) and hand-foot syndrome (16.4% vs 15.2%) in the pyrotinib vs. Tykerb arms, respectively. No grade 4 or 5 side effects occurred in either arm. However, as the study progressed, Xu said, the incidences of diarrhea were low severity, short in duration, and rarely led to treatment termination.

In the pyrotinib group, 61 patients discontinued treatment, including 53 for disease progression and 44 due to side effects; while 101 patients in the Tykerb arm discontinued treatment, including 95 for disease progression and three due to side effects. At the time of data analysis, 73 patients had decided to continue with treatment, compared to 31 patients in the Tykerb group

A version of this story originally appeared on OncLive® as “Pyrotinib Combo Improves PFS in HER2+ Metastatic Breast Cancer.”