Dr. Chien on Tucatinib in HER2+ Breast Cancer

A. Jo Chien, MD, associate clinical professor, Department of Medicine, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discusses the use of tucatinib (ONT-380) in the treatment of patients with HER2-positive breast cancer.

Tucatinib is one of many TKIs that possesses the potential to penetrate the blood—brain barrier, says Chien. In addition to tucatinib, lapatinib (Tykerb) and neratinib (Nerlynx) have also been looked at in the treatment of patients with brain metastases. As single agents, they have not demonstrated compelling responses, but when paired with capecitabine, these agents have shown impressive responses in the central nervous system, says Chien.

Tucatinib has also shown strong responses when paired with trastuzumab (Herceptin) and capecitabine. The unique aspect of tucatinib is that it has more preferential binding to HER2 than EGFR, and therefore, has lower rates of diarrhea, explains Chien. An issue with the TKIs has been the associated gastrointestinal toxicity. If tucatinib continues to show a safety profile that is consistent with what has been observed to date, it could fulfill a large unmet need for patients.