Results from a phase II clinical trial presented at the San Antonio Breast Cancer Symposium (SABCS), being held December 10?14, 2013 in San Antonio, Texas, shows that adding dasatinib (Sprycel?; Bristol-Myers Squibb Company)
to a standard anti-hormone therapy, letrozole (Femara?; Novartis), doubled the time before disease progressed for women with hormone receptor-positive, HER2-negative metastatic breast cancer or MBC.[1]
In the United States, dasatinib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic myelogenous leukemia or CML. The drug works by blocking the activity of a protein called Src, a non-receptor protein tyrosine kinase that plays a multitude of roles in cell signaling and is involved in the control of many functions, including cell adhesion, growth, movement and differentiation. Recently, Src has been implicated in the spread of ER+ breast cancer to bones.
?Patients with metastatic breast cancer desperately need new treatment options that can lengthen and improve the quality of their lives,? noted Devchand (Dev)Paul, D.O., Ph.D., breast oncologist at U.S. 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 compared with letrozole alone.”
Adding dasatinib to letrozole improves progression-free survival for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer…
?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 added.
Paul and colleagues enrolled 120 postmenopausal women with locally recurrent or metastatic hormone receptor-positive, HER2-negative breast cancer in the phase II 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.
The clinical-benefit rate is 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 six or more months.
The researchers found that adding dasatinib to letrozole did not increase the clinical-benefit rate compared with letrozole alone. When a second measure of the study?s outcome was analyzed, the combination therapy was shown to dramatically improve progression-free survival. Progression-free survival 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,? Paul concluded.
This study was supported by funds from Bristol-Myers Squibb. Paul declared no conflicts of interest.
For more information:
[1] Paul D, Vukelja SJ, Holmes FA, Blum J, McIntyre KJ, Kumar AR, Lindquist DL, et al. Letrozole plus dasatinib improves progression-free survival (PFS) in hormone receptor-positive, HER2-negative postmenopausal metastatic breast cancer (MBC) patients receiving first-line aromatase inhibitor (AI) therapy. Publication Number: S3-07. Presented by Dev Paul, D.O., Ph.D.
[2] NCT00696072 – Randomized Phase II Trial of Letrozole With or Without Dasatinib as First and Second-line Treatment for Hormone Receptor-positive, HER2-negative Post-menopausal Breast Cancer That is Unresectable, Locally Recurrent or Metastatic [Study Record Detail]
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