Adding the drug dasatinib to the standard antihormone therapy, letrozole, doubled the time before disease progressed for women with hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative metastatic breast cancer. These results of a phase 2 clinical trial were presented at the 2013 San Antonio Breast Cancer Symposium, December 10-14, 2013.

Dasatinib is approved by the FDA for the treatment of chronic myelogenous leukemia. One of the ways it works is by blocking the activity of a protein called Src, which has been recently implicated in the spread of breast cancer to bones.

“Patients with metastatic breast cancer desperately need new treatment options that can lengthen and improve the quality of their lives,” said Dev Paul, DO, PhD, breast oncologist at US Oncology and Rocky Mountain Cancer Centers in Denver, Colorado. “Because several studies have linked high levels of Src activity to breast cancer metastasis to the bone, we wanted to see whether combining letrozole and dasatinib as first-line treatment for metastatic breast cancer would improve the clinical-benefit rate and progression-free survival (PFS) compared with letrozole alone.

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“We are encouraged to see that the combination doubled progression-free survival time,” he added. “But this was a small study, and we really need a biomarker to measure Src activity in breast tumors, so that we can better determine which patients will be most likely to benefit from the addition of dasatinib to letrozole.”

Paul and colleagues enrolled 120 postmenopausal women with locally recurrent or metastatic hormone receptor-positive, HER2-negative breast cancer in the phase 2 clinical trial. They randomly assigned 63 participants to letrozole and 57 to letrozole plus dasatinib. The primary aim of the study was to determine whether adding dasatinib to letrozole increased the clinical benefit rate (CBR). The CBR rate is based on the number of patients who had a complete response, plus the number who had a partial response, plus the number who had stable disease for 6 or more months.

The researchers found that adding dasatinib to letrozole did not increase the CBR compared with letrozole alone. When a second measure of the study’s outcome was analyzed, the combination therapy was shown to dramatically improve PFS. PFS for patients receiving dasatinib and letrozole was 20.1 months compared with 9.9 months for letrozole alone.

Patients receiving dasatinib plus letrozole did experience additional side effects but none were considered severe adverse events, according to Paul, and most patients tolerated the full dose of dasatinib.

“Although these data suggest that adding dasatinib to letrozole improves progression-free survival for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer, we would like to find a biomarker for Src activity in the breast before conducting larger clinical studies of this drug combination,” concluded Paul.