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.

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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 de-escalation strategies for patients with HER2-positive breast cancer.

The first approach is looking at de-escalating chemotherapy, says Chien. Physicians used to give aggressive regimens containing anthracyclines. Though the BCIRG 006 study was not powered to look at this, physicians saw very similar long-term outcomes out to 10 years between non-anthracycline and anthracycline-based chemotherapies. In the APT study in patients with stage I node-negative tumors, physicians saw long-term outcomes with disease-free survival rates of 94% at 7 years of follow-up.

Another approach is looking at the duration of trastuzumab (Herceptin). Physicians know that patients do not benefit from more than 1 year of trastuzumab, but because 1 year was chosen arbitrarily, it may be worth investigating lower durations, explains Chien. Moreover, giving just hormone therapy with either trastuzumab or a small molecule tyrosine kinase inhibitor is being investigated, as a subset of those patients will achieve complete responses without chemotherapy.

Dr. Chien on De-Escalation Strategies for Patients With HER2-Positive Breast Cancer

A. Jo Chien, MD, associate clinical professor, Department of Medicine, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discusses treatment duration in HER2-positive breast cancer.

Optimal treatment duration for patients with early-stage HER2-positive breast cancer is a big area of discussion, says Chien. In the field, there are challenges in identifying which patients can get away with less treatment and those who remain at high-risk despite use of trastuzumab (Herceptin), adds Chien.

Despite trastuzumab, approximately 1/4 of patients will relapse and need subsequent therapy. There are a number of new agents that have entered the field, such as pertuzumab (Perjeta) and neratinib (Nerlyx) that can be used in the early-stage setting.

On the other hand, there are also patients who are being overtreated, notes Chien. Historical studies were done in patients with high-risk disease, including positive lymph nodes and larger tumors. Those with node-negative disease and smaller tumors may not need as intensive treatment, states Chien.

A. Jo Chien, MD

Articles

Dr. Chien on Tucatinib in HER2+ Breast Cancer

Dr. Chien on De-Escalation Strategies for Patients With HER2-Positive Breast Cancer

Dr. Chien on Treatment Duration in HER2+ Breast Cancer