Tucatinib Shows Clinical Benefit in Phase I Trial in HER2-Positive Breast Cancer
Phase I clinical trial data published by Moulder-Thompson et al in Clinical Cancer Research reported that the investigational anticancer agent tucatinib (formerly ONT-380) showed 'notable activity' in the treatment of HER2-positive breast cancer with . The 50 women treated had disease progression despite a median of 5 previous treatment regimens. Of these heavily pretreated patients, 27% saw clinical benefit from the drug, with at least “stable disease” at 24 or more weeks after the start of treatment.
These data led to two subsequent phase Ib studies, resulting in tucatinib earning U.S. Food and Drug Administration (FDA) Fast Track status and the expansion of this clinical trial.
“Usually we expect the results of a phase I clinical trial to give us data that we can use to guide the results of future treatments. This is a great case in which, for many of these patients, the results were immediate. There are women who are alive today because of this drug,” said Virginia Borges, MD, MMSc, Director of the Breast Cancer Research Program and Young Women's Breast Cancer Translational Program at the University of Colorado (CU) Cancer Center. Dr. Borges has been a major driver of the drug's development from its invention at Array Biopharma through clinical trials of the drug, which is licensed to Cascadian Therapeutics.
About Tucatinib
Tucatinib is a small-molecule inhibitor of the HER2 growth factor receptor. The drug works by targeting HER2 tyrosine kinase—a link in the chain of communication that allows HER2 receptors to signal the growth of the cell. Small-molecule drugs are able to pass through the blood-brain barrier to act against brain metastases of the disease. HER2-positive breast cancer is more likely to affect younger women and also more likely than other breast cancers to metastasize specifically to the brain.
Working with Dr. Borges's Young Women's Breast Cancer Translational Program at CU Cancer Center, Elena Shagisultanova, MD, PhD, recently earned a $1.4 million competitive ASPIRE grant to conduct a clinical trial exploring the use of tucatinib against triple-positive breast cancer, which is driven by both estrogen and progesterone receptors and the HER2/neu oncogene.
“When both [estrogen and HER2] are positive, they counteract the therapy aimed at one or the other…,” Dr. Borges said. More specifically, when both avenues are present, the crosstalk leads to tumors being resistant to treatment, as either avenue can allow the cancer to survive therapy. Previous trials concurrently targeting estrogen and HER2 have been, according to Dr. Borges, “lackluster,” resulting in no changes to the standard of care.
The forthcoming trial led by Dr. Shagisultanova will be a multicenter clinical trial with CU Cancer Center as the lead site, testing the combination of three drugs—tucatinib plus the antiestrogen receptor drug letrozole and the cell-cycle inhibitor palbociclib (Ibrance)—against breast cancers positive for both HER2 and estrogen receptors.
Future Studies
“Tucatinib could be a substantially practice-changing drug,” Dr. Borges said, meaning that in addition to current investigations of the drug as a third-, fourth-, or more-than-fifth-line treatment, she envisions its use sooner in the arc of breast cancer treatment and with far more patients.
“It's going to be an especially important drug due to its ability to control brain metastases,” she predicted. “The opportunity to study it as a front-line drug for recurrent triple-positive breast cancer could even someday help us prevent or delay these brain metastases.”
Because the drug is taken in pill form and has a very favorable side-effect profile, Dr. Borges pointed out that it is relatively patient-friendly, allowing women to avoid treatments in infusion centers and also many of the side effects associated with chemotherapies.
Ongoing research updates for tucatinib are expected in journals and meetings later in 2017.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
