Twenty years ago, no targeted treatments existed for breast cancers with high levels of a protein called HER2 (HER2-positive, or HER2+). The significance of HER2 in breast cancer had only been recognized in 1987, when excessive levels of the protein were identified in about 20% of breast cancers. Oncologists realized that high levels of HER2 mark a type of cancer with a poor prognosis, as compared to the predominant type of breast cancer: estrogen receptor-positive, HER2 negative (HER2-).
The possibility of targeting HER2 to treat cancer was fulfilled in 1998, when the U.S. Food and Drug Administration (FDA) approved Herceptin (generic name trastuzumab), for treatment of metastatic HER2+ breast cancer. Made by Genentech, Herceptin is a type of drug known as a humanized antibody, meaning that it mimics an immune system attack on tumor cells, specifically those with high levels of HER2. Now, 20 years later, it is easier to appreciate the significance of this drug, which literally changed the lives of many HER2+ breast cancer patients, and continues to do so today. Continue reading…
“Tucatinib used in combination with capecitabine, trastuzumab (Herceptin), or both agents showed promising antitumor activity in heavily pretreated women with HER2-positive breast cancer with or without brain metastases, according to findings published in The Lancet Oncology.
“In phase Ib results from a nonrandomized, open-label study, 83% (5/6) of patients with measurable disease treated with tucatinib/capecitabine had an objective response, as did 40% (6/15) of patients receiving tucatinib/trastuzumab. Sixty-one percent (14/23) of patients treated with the combination of all 3 drugs had an objective response.”
“The FDA granted orphan drug designation to tucatinib for the treatment of patients with breast cancer whose disease metastasized to the brain, according to the drug’s manufacturer.
“Tucatinib (ONT-380, Cascadian Therapeutics) is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER-2 without significant inhibition of EGFR, which has been associated with significant toxicities.”
University of Colorado Cancer Center | Jan 10, 2017
“Phase 1 clinical trial data published this week in the journal Clinical Cancer Research show early promise of the investigational anti-cancer agent tucatinib (formerly ONT-380) against HER2+ breast cancer. The 50 women treated had progressed despite a median 5 previous treatment regimens. Twenty-seven percent of these heavily pretreated patients saw clinical benefit from the drug, with at least ‘stable disease’ at 24 or more weeks after the start of treatment. These data have led to two subsequent Phase Ib studies, resulting in tucatinib earning FDA fast-track status and the expansion of this study once meant only to demonstrate drug safety into the “pivotal” trial that will determine approval.”
“Breast cancer patients sometimes end up dying when their tumors spread all the way to the brain. Some very good drugs already exist for patients with breast cancer, especially ones with tumors that overexpress the HER2 marker, but that success has raised a new question: Can drugmakers take another step, and fight those deadly brain metastases that get people in the end?
“Seattle-based Cascadian Therapeutics is testing that idea this week with researchers gathered at the San Antonio Breast Cancer Symposium. Cascadian is reporting today that patients who got conventional capecitabine and trastuzumab, plus an experimental small-molecule drug, tucatinib (aka ONT-380), lived a median of 7.8 months without their tumors getting worse. About 61% of patients on that triple-drug combo saw tumors shrink. It’s an impressive result, given that these patients were especially ill when they enrolled in the study, having already received a median of three prior rounds of HER2-targeted therapy. The data are also holding up over time: a snapshot of the data from June showed patients living a median of 6.3 months without their tumors spreading.”