Conference Coverage

Pyrotinib bests lapatinib in HER2+ metastatic breast cancer



The combination of pyrotinib and capecitabine significantly prolonged progression-free survival (PFS), when compared with lapatinib and capecitabine, among patients with previously treated HER2-positive metastatic breast cancer in a phase 3 trial.

PFS was extended by nearly 6 months among patients who received pyrotinib, a novel pan-HER2 inhibitor, combined with capecitabine. Grade 3 diarrhea occurred in nearly 31% of patients receiving the pyrotinib-capecitabine combination, though none of the patients discontinued treatment due to this adverse event.

Binghe Xu, MD, PhD, of the National Cancer Center/Cancer Hospital at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, presented these results, from the phase 3 PHOEBE trial, as part of the American Society of Clinical Oncology virtual scientific program.

The value of pyrotinib

Although there are already many targeted therapies for HER2-positive metastatic breast cancer, accessibility can be an issue, with drugs such as pertuzumab and trastuzumab emtansine (T-DM1) not available in all regions of the world, according to Dr. Xu.

“Before we initiated this clinical trial, lapatinib plus capecitabine was the only second-line standard of care against HER2-positive metastatic breast cancer in China,” he said.

Based, in part, on results of the PHOEBE trial, the combination of pyrotinib and capecitabine was approved in China as a second-line standard of care for patients with HER2-positive metastatic breast cancer, according to Dr. Xu.

Pyrotinib has now demonstrated “clinical value” in two phase 3 clinical trials, but its value in relation to pertuzumab, T-DM1, tucatinib, trastuzumab deruxtecan, or neratinib is less clear, said Aleix Prat, MD, PhD, of Hospital Clinic of Barcelona.

“Also, in my opinion, the toxicity profile needs attention,” Dr. Prat said in a discussion of the PHOEBE results that was also part of the virtual ASCO meeting.

The 31% incidence of grade 3 diarrhea was “very similar,” he said, to what was seen in PHENIX, another phase 3 trial of pyrotinib plus capecitabine that was presented at the 2019 ASCO annual meeting (J Clin Oncol 37, 2019 suppl; abstr 1001).

“What is the current therapy landscape? In my opinion, today, the first line remains taxane, trastuzumab, and pertuzumab; the second line T-DM1; and the third line tucatinib, trastuzumab, and capecitabine, with other treatment strategies reserved for later lines,” Dr. Prat said.


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