Researchers are reporting clinical activity with the investigational oral compound tucatinib, used as part of combination therapy in patients with advanced breast cancer and skin metastases.
The findings, from a small group of patients enrolled in a Phase Ib study, were presented at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen, Denmark.
Dr. Alison Conlin, a medical oncologist at Providence Cancer Center in Portland, OR, and colleagues reported outcomes in eight women with human epidermal growth factor receptor-positive (HER2-positive) metastases to the skin, who were treated with the maximum tolerated dose of tucatinib combined with capecitabine and/or trastuzumab.
Tucatinib – also called ONT-380 – is a potent selective small molecule inhibitor of HER2.
Cutaneous metastases have been estimated to occur in approximately 25 percent of women with metastatic breast cancer and are often the first sign of extranodal metastatic disease. Their frequency is thought to be even higher in the presence of HER2 overexpression.
Investigators have hypothesized that skin, like the central nervous system, may represent a sanctuary site for breast cancer cells during treatment with anti-HER2 antibodies.
Notably, skin metastases are a difficult site of disease control in women with HER2-overexpressing metatastic breast cancer. At present, there is no approved therapy for such lesions in these patients.
Tucatinib led to significant reductions in skin lesions
Study participants had undergone prior treatment with trastuzumab, taxane, and trastuzumab emtansine. Most of them had also been treated with lapatinib, pertuzumab, and/or radiation to the chest wall/skin. Patients had received a median of six prior lines of therapy.
One patient had a complete response after tucatinib treatment, defined as a disappearance of all skin lesions. Three patients had partial responses, defined as a greater than 30 percent reduction in the sum of diameters of all target skin lesions from baseline. The remaining four patients had stable disease.
"We observed great responses in the skin in our patients with metastatic breast cancer and skin metastases who were treated with tucatinib and either trastuzumab, capecitabine, or all three drugs in combination.
The skin is a very morbid and difficult area of disease for women with metastatic breast cancer with a resulting profound impairment in their quality of life, and therefore response in this difficult area to treat is needed."
The study was conducted by teams from multiples sites in the United States, including the Providence Cancer Center in Portland, and the University of Colorado in Aurora, and the MD Anderson Cancer Center in Houston.
This article was originally published at the “Article” source noted above and distributed by The Tutu Project for informational purposes only.
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