Entry Detail
| General information | |
| Database: | DB00202 |
| Objective: | Src kinasemediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a firstline chemotherapy for metastatic castrationresistant prostate cancer. they assessed whether dasatinib plus docetaxel in chemotherapynaive men with metastatic castrationresistant prostate cancer led to greater efficacy than with docetaxel alone. |
| Authors: | Araujo JC, et al |
| Title: | Docetaxel and dasatinib or placebo in men with metastatic castrationresistant prostate cancer (READY): a randomised, doubleblindphase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2013 |
| PMID: | 24211163 |
| Trial Design | |
| Clinical Trial Id: | NCT00744497 |
| Agent: | dasatinib |
| Target: | Protooncogene tyrosineprotein kinase SRC Abl Protooncogene tyrosineprotein kinase LCK Protooncogene tyrosineprotein kinase Fyn |
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Docetaxel +dasatinib |
| Study Type: | a doubleblind, randomised, placebocontrolledphase III study |
| Key Patients Feature: | men of 18 years or older with chemotherapynaive, metastatic, castrationresistant prostate cancer, and adequate organ function from 186 centres across 25 countries |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | Docetaxel+placebo |
| Treatment Info: | Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m(2) intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (01 vs 2), bisphosphonate use (yes vs no), and urinary Ntelopeptide (uNTx) value (<60 ¦Ìmol/mol creatinine vs more than and equal to 60 ¦Ìmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. |
| Primary End Point: | overall survival, analysed by intention to treat. |
| Secondary End Point: | NA |
| Patients Number: | 1522 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 914 patients had died. Median overall survival was 21.5 months (95% CI 20.322.8) in the dasatinib group and 21.2 months (20.023.4) in the placebo group (stratified [HR] 0.99, 95.5% CI 0.871.13; p=0.90). |
| Adverse Event(agent arm): | The most common grade 34 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 34 pleural effusions were uncommon (ten [1%] vs three [<1%]). |
| Conclusions: | The addition of dasatinib to docetaxel did not improve overall survival for chemotherapynaive men with metastatic castrationresistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. |