SAN ANTONIO—Adding dasatinib to first-line letrozole aromatase inhibitor (AI) therapy appears to be associated with delayed disease progression among women with hormone receptor–positive, HER2-negative metastatic breast cancer, reported authors of a small, nonrandomized exploratory phase 2 clinical trial presented at the 2013 San Antonio Breast Cancer Symposium.

“We are encouraged to see that the combination doubled progression-free survival (PFS) time,” said study author Dev Paul, DO, PhD, a breast oncologist at US Oncology and Rocky Mountain Cancer Centers, in Denver, CO. “These findings suggest that dasatinib may inhibit the emergence of acquired resistance to AI therapy.”

However, Dr. Paul was quick to add that the encouraging results were based on a small study and that an Src activity biomarker is needed.

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Dasatinib is a U.S. Food and Drug Administration–approved treatment for chronic myelogenous leukemia (CML). It blocks Src protein tyrosine kinase activity, which is believed to be involved in estrogen receptor(ER)–positive breast tumor metastasis to bone.

A total of 120 postmenopausal women with locally recurrent or metastatic, ER-positive, HER2-negative breast cancer were randomly assigned to receive oral letrozole (2.5 mg every day; n = 63) or letrozole plus dasatinib (100 mg/day; n = 57). Patients who progressed on letrozole (n = 35) were allowed to cross over to receive dasatinib.

Although dasatinib was not associated with improved response rates, the combination drug therapy was associated with a “promising” median PFS of 20.1 months compared with 9.9 months among women in the letrozole-only study arm (hazard ratio [HR], 0.69; P = 0.05), Dr. Paul reported. “This hazard ratio is exploratory.”

“Dasatinib may decrease incidence of osteopenia on AI therapy,” Dr. Paul said.

Grade 2 and 3 toxicities were rare among patients in the letrozole-only study arm.

“There were no unexpected or grade 4 toxicities reported” in the dasatinib arm, he noted. The most common adverse treatment-related events among patients in the dasatinib study arm included grade 2 fatigue (n = 8; 14%), grade 2 nausea (n = 7; 12%), neutropenia (n = 5; 9%) and rash (n = 5; 9%).

Dasatinib dose reductions were necessary in 27% of patients but daily dasatinib at 100 mg “was generally well tolerated with no unexpected toxicities,” Dr. Paul reported.

“Patients with metastatic breast cancer desperately need new treatment options that can lengthen and improve the quality of their lives,” Dr. Paul said—but researchers need to identify an Src activity biomarker before undertaking a larger clinical study of dasatinib plus letrozole drug therapy, he added.

The study was funded by Bristol-Myers Squibb.


  1. Paul D et a. S3-07. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.