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Overall survival (OS) and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): Results from the randomized phase III READY trial.

Publication ,  Journal Article
Trudel, GC; Saad, F; Armstrong, AJ; Yu, EY; Bellmunt, J; Wilding, G; McCaffrey, J; Serrano, SV; Matveev, V; Efstathiou, E; Oudard, S; Sizer, B ...
Published in: J Clin Oncol
February 20, 2013

LBA8 Background: SRC kinases may contribute to androgen independence of mCRPC.Dasatinib (DAS) inhibits tyrosine kinases including SRC kinases with preclinical evidence for antimetastatic activity, inhibition of osteoclast function in tumor microenvironment, and synergistic activity with docetaxel (D). In phase I/II trials of mCRPC patients (pts), DAS in combination with D had an acceptable safety profile with objective response rates (ORR) improved over historical data and decreased levels of bone turnover markers. METHODS: READY was a multinational, randomized, double-blinded, placebo-controlled, phase III study. Pts with mCRPC (n = 1,522) were randomized (1:1) to receive either D 75 mg/m(2)q3wk + prednisone with double-blinded DAS 100 mg qd (DAS/D, n = 762) or placebo (PBO/D, n = 760). Primary endpoint was overall survival (OS). Secondary endpoints were ORR, time to first skeletal-related event (TFSRE), time to prostate-specific antigen progression (TPSAP), urinary N-telopeptide (uNTX) reduction, pain reduction, progression-free survival (PFS), and safety. RESULTS: No OS difference between DAS/D and PBO/D (median, 21.5 vs. 21.2 mos; hazard ratio [HR], 0.99; log-rank P = 0.90) was observed. Results of secondary endpoints for DAS/D vs. PBO/D were: ORR (30.5 vs. 31.9%); TFSRE (median, not reached vs. 31.1 mos; HR, 0.81 [95% CI, 0.64-1.02]); uNTX reduction (66.0 vs. 60.6%); PFS (median, 11.8 vs. 11.1 mos; HR, 0.92); TPSAP (median, 8.0 vs. 7.6 mos; HR, 0.91), and pain reduction (66.6 vs. 71.5%). Twenty-three percent of DAS/D and 14% of PBO/D pts received therapy for <3 mos. Most common AEs in DAS/D arm included diarrhea, fatigue, alopecia, and nausea. Grade 3-4 AEs of interest for DAS/D vs. PBO/D included anemia (8.0 vs.5.9%), neutropenia (6.2 vs. 5.5%), hypocalcemia (3.5 vs.3.1%), GI bleeding (2.6 vs.1.3%), and pleural effusion (1.3 vs. 0.4%). CONCLUSIONS: The addition of DAS to standard-of-care chemotherapy in mCRPC pts did not improve OS. There was a modest reduction in the risk of TFSRE with DAS/D vs. PBO/D. With a median follow-up of 19 mos of 761 DAS/D-treated pts, no unexpected toxicities for DAS were observed. CLINICAL TRIAL INFORMATION: NCT00744497.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 20, 2013

Volume

31

Issue

6_suppl

Start / End Page

LBA8

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

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Trudel, G. C., Saad, F., Armstrong, A. J., Yu, E. Y., Bellmunt, J., Wilding, G., … Logothetis, C. (2013). Overall survival (OS) and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): Results from the randomized phase III READY trial. J Clin Oncol, 31(6_suppl), LBA8. https://doi.org/10.1200/jco.2013.31.6_suppl.lba8
Trudel, G. C., F. Saad, A. J. Armstrong, E. Y. Yu, J. Bellmunt, G. Wilding, J. McCaffrey, et al. “Overall survival (OS) and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): Results from the randomized phase III READY trial.J Clin Oncol 31, no. 6_suppl (February 20, 2013): LBA8. https://doi.org/10.1200/jco.2013.31.6_suppl.lba8.
Trudel GC, Saad F, Armstrong AJ, Yu EY, Bellmunt J, Wilding G, McCaffrey J, Serrano SV, Matveev V, Efstathiou E, Oudard S, Morris MJ, Sizer B, Goebell PJ, De Bono JS, Paliwal P, Durham S, Cheng S, Logothetis C. Overall survival (OS) and safety of dasatinib/docetaxel versus docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): Results from the randomized phase III READY trial. J Clin Oncol. 2013 Feb 20;31(6_suppl):LBA8.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

February 20, 2013

Volume

31

Issue

6_suppl

Start / End Page

LBA8

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences