ORLANDO – Adding dasatinib to standard-of-care chemotherapy led to a modest delay in skeletal-related events but did not improve overall survival for patients with metastatic castrate-resistant prostate cancer in the READY trial.
Dasatinib, a tyrosine kinase inhibitor, showed promising results in phase I and II studies, but fell short in READY, a multinational randomized double-blinded, placebo-controlled study, sponsored by Bristol-Myers Squibb.
Dr. John C. Araujo
With no difference in overall survival and no meaningful changes in the study\'s secondary endpoints, the search continues for treatments for this group of patients whose current options are mostly palliative with modest improvements in survival. The observed delay in skeletal-related events with dasatinib (Sprycel) is being further investigated, said the study’s lead author, Dr. John C. Araujo of the University of Texas MD Anderson Cancer Center, Houston.
In READY, 1,522 patients were randomized to receive docetaxel (75 mg/m2, three times a week) plus prednisone and either 100 mg daily of dasatinib (762 patients), or placebo (760 patients).
There were no meaningful differences in the demographics or disease characteristics of the two study arms. Patients were treated until disease progression or they had unacceptable toxicity.
The primary endpoint of the study was overall survival. The secondary endpoints were objective response rates, time to first skeletal-related event, time to prostate-specific antigen progression, urinary N-telopeptide (uNTx) reduction, pain reduction, progression-free survival, and safety.
Overall survival was 21.5 months in the dasatinib group and 21.2 months in the placebo group (hazard ratio, 0.99; P = .90). Comparably similar outcomes were seen in secondary endpoints for dasatinib vs. placebo arm: objective response rates were 30.5% and 31.9%, respectively; median time to prostate-specific antigen progression was 8 months vs. 7.6 months; uNTx reduction was 66% v. 60.6%; pain reduction was 66.6% v. 71.5%; progression-free survival was 11.8 months v. 11.1 months.
The one exception was median time to first skeletal event, which was not reached in the dasatinib group and was in 31.1 months for the placebo group.
Dr. William Oh, chief of hematology and medical oncology at Tisch Cancer Institute and the Mount Sinai School of Medicine, New York, commented that "about two-thirds of the patients were not on bisphosphonates, which may explain why there was a trend toward a benefit in terms of (skeletal-related events)" in the dasatinib arm.
Dr. Araujo reported there were no unexpected safety findings and no unanticipated events. Patients came off the trial for similar reasons in both arms, including disease progression and maximum clinical benefit. Adverse events related to treatment included diarrhea, fatigue, alopecia, and nausea and occurred in 18% of patients in the dasatinib arm and in 9% in the placebo arm. Grade 3-4 adverse events of interest included anemia (8% vs. 5.9% in placebo), neutropenia (6.2 % vs. 5.5%), hypocalcemia (3.5% vs. 3.1%), gastrointestinal bleeding (2.6% vs. 1.3%), and pleural effusion (1.3 vs. 0.4%).
Dr. Araujo has received research funding from Bristol-Myers Squibb, the maker of Sprycel and sponsor of the trial. Dr. Oh has been consultant or adviser for Amgen, Astellas Pharma, Bayer, Bellicum Pharmaceuticals, Dendreon, Janssen Biotech, Medivation, and Pfizer. He has received research funding from Millennium.
The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.