Pyrotechnic.

Top Line: What HER2-targeted therapies are available for progressive, metastatic HER2+ breast cancer?

The Study: A challenge with progressive, metastatic HER2+ breast cancer is that you can’t just stop HER2-blockade. Therefore, further lines of HER2 targeted therapies are needed after patients progress on standard first-line targeted therapies. One such regimen is lapatinib and capecitabine. However, lapatinib is a reversible blocker of HER2 phosphorylation--meaning resistance is a problem. Pyrotinib is an irreversible tyrosine kinase inhibitor of HER1, HER2, and HER4. In this phase 2 trial, women with metastatic HER2+ breast cancer after multiple lines of systemic therapy were randomized to receive capecitabine with either lapatinib or pyrotinib. Importantly, the trial was performed in Chinese centers with different access to HER2 targeted therapies. As a result, only about half of patients had ever received trastuzumab and none received prior pertuzumab or trastuzumab emtansine. On independent radiology review, the objective response rate was 22% higher with pyrotinib (71%) compared to lapatinib (49%). Median progression-free survival was 18 months with pyrotinib compared to 7 months with lapatinib. That improvement was significant for both trastuzumab-refractory and trastuzumab-naive sub-groups. Diarrhea and hand-foot syndrome were major toxicities experienced by 15% and 25% of patients on pyrotinib.

TBL: Pyrotinib, a pan-ErbB tyrosine kinase inhibitor, has a 22% higher response rate than lapatinib when combined with capecitabine in women with metastatic HER2+ breast cancer. | Ma, J Clin Oncol 2019