Results of clinical trials of tucatinib with T-DM1 show promise in the treatment of breast cancer HER2 +

July 11, 2018

The results of Phase 1b clinical trials published in JAMA Oncology are promising for the combination of tucatinib (formerly ONT-380) with T-DM1 against HER2-positive bad cancer, highly pretreated. Of the 57 patients treated, 48 percent responded to the combination, with a median cancer control of 8.2 months. It is important to note that tucatinib acted against brain metastases derived from bad cancer HER2 +, one of the main causes of mortality from the disease.

"At the University of Colorado Cancer Center, we have been working with this drug since it was discovered by ARRAY BioPharma in Boulder, first it was ARRAY-380, then ONT-380 and now it is called tucatinib. He has strived to take it to trials and now in places where we see it provide a real benefit to women, "says Virginia Borges, MD, MMSc, ​​director of the Breast Cancer Research Program and Breast Cancer Translation Program. of Young Women in CU Cancer Center.

About 20 percent of bad cancers are considered HER2-positive, which means that these cancer cells overexpress "receptors" that bind human epidermal growth factor 2 (HER2). When HER2 receptors in cancer cells trap HER2, it signals the uncontrolled reproduction of these cells. However, the opposite is also true: when HER2 + bad cancer cells can not bind to HER2, they die.

Tucatinib is a small molecule inhibitor of the growth factor receptor HER2. The drug acts by focusing on the "tyrosine kinase" HER2, a link in the chain of communication that allows HER2 receptors to signal the growth of the cell. It is important to note that the fact that it is a small molecule means that the drug can pbad through the blood-brain barrier to act against brain metastases of the disease. Breast cancer HER2 + is more likely to affect younger women and also other types of bad cancer that specifically metastasize to the brain.

"One of the best things about this medication is that it combines well with almost everything," he admitted, "when you try tucatinib in combination with other drugs, it feels like you just administered the other drug." It's a pill. And it hardly causes side effects, it's really a doctor's dream, "says Borges. [19659003EnconsecuenciaeltucatinibseestáevaluandoenotrosensayosyconsociosadicionalesporejemplootroensayoofrecidoenCUCancerCenteryenotroslugaresqueexploranelusodelfármacocomocomponentedeunacombinacióncontraelllamadocáncerdemamatriplepositivo(aquelloscánceresqueexpresanreceptoresdeestrógenoprogesteronayHER2)Borgesesperaquelaefectividaddetucatinibenpacientesconenfermedadmetastásicaquehanprobadotratamientospreviospuedaconduciraensayosdelmedicamentoutilizadoanteriormenteenelcursodeltratamiento

In the current trial, the tucatinib combined with Ado-Trastuzumab Emtansine (T -DM1), which is one of a clbad of drugs known as antibody-drug conjugates. In this case, an antibody called trastuzumab that binds to HER2 is combined with a drug called emtansin that kills the cells. Together, T-DM1 delivers the drug that kills cells directly to cancer cells labeled with HER2.

"It is a regimen without chemotherapy, once the drug is approved, we hope to see this regimen advance in the course of treatment, and in the end, we hope it will prevent recurrences and also decrease the number of metastatic cerebral recurrences," says Borges. .

Updated results will be presented at the San Antonio Breast Cancer Symposium in December 2018.

Source: -tucatinib-with-t-dm1-against-her2-bad-cancer /


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