TY - JOUR
T1 - Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421)
T2 - A randomised phase 3 trial
AU - Quinn, David I.
AU - Tangen, Catherine M.
AU - Hussain, Maha
AU - Lara, Primo N.
AU - Goldkorn, Amir
AU - Moinpour, Carol M.
AU - Garzotto, Mark G.
AU - Mack, Philip C.
AU - Carducci, Michael A.
AU - Monk, J. Paul
AU - Twardowski, Przemyslaw W.
AU - Van Veldhuizen, Peter J.
AU - Agarwal, Neeraj
AU - Higano, Celestia S.
AU - Vogelzang, Nicholas J.
AU - Thompson, Ian M.
N1 - Funding Information:
The investigation was supported, partly, by the following Public Health Service Cooperative Agreement grant numbers awarded by the National Cancer Institute, Department of Health and Human Services: CA32102, CA38926, CA46368, CA46441, CA58882, CA58861, CA12644, CA22433, CA46282, CA27057, CA58416, CA45807, CA45808, CA45450, CA42777, CA35281, CA20319, CA35090, CA76429, CA14028, CA67575, CA45377, CA68183, CA63848, CA74647, CA16385, CA35192, CA63844, CA11083, CA63845, CA76447, CA35128, CA13612, CA35431, CA76448, CA35178, CA35176, CA35119, CA35421, CA128567, CA04919, CA68183, CA45560, CA37981, CA58723, CA21115, CA16116, and CA31949; and, partly, by Sanofi-Aventis and Abbott Laboratories. The authors report on behalf of a large team and would like to acknowledge the contribution of clinicians, research teams, patients, and their families through ECOG, CALGB, and the Clinical Trials Support Unit in completing SWOG S0421.
PY - 2013/8
Y1 - 2013/8
N2 - Background: The endothelin pathway has a role in bone metastases, which are characteristic of advanced prostate cancer. Atrasentan, an endothelin receptor antagonist, has shown activity in prostate cancer. We therefore assessed its effect on survival in patients with castration-resistant prostate cancer with bone metastases. Methods: In a double-blind phase 3 trial, men with metastatic castration-resistant prostate cancer, stratified for progression type (prostate-specific antigen or radiological), baseline pain, extraskeletal metastases, and bisphosphonate use, were randomly assigned in a 1:1 ratio to docetaxel (75 mg/m2 every 21 days, intravenously) with atrasentan (10 mg/day, orally) or placebo for up to 12 cycles and treated until disease progression or unacceptable toxicity. Patients who did not progress on treatment were permitted to continue atrasentan or placebo for up to 52 weeks. Coprimary endpoints were progression-free survival (PFS) and overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00134056. Findings: 498 patients were randomly assigned to the atrasentan group and 496 to the placebo group. The trial was halted early for futility in April, 2011, after a planned interim analysis. Median PFS was 9·2 months (95% CI 8·5-9·9) in the atrasentan group and 9·1 months (8·4-10·2) in the placebo group (hazard ratio 1·02, 0·89-1·16; p=0·81). Median overall survival was 17·8 months (16·4-19·8) in the atrasentan group versus 17·6 months (16·4-20·1) in the placebo group (1·04, 0·90-1·19; p=0·64). 278 (57%) of 492 patients in the atrasentan group had grade 3 and greater toxicity compared with 294 (60%) of 486 in the placebo group (p=0·22). Three deaths in the atrasentan group and seven in the placebo group were judged to be possibly or probably due to protocol treatment. Interpretation: Atrasentan, when added to docetaxel, does not improve overall survival or PFS in men with castration-resistant prostate cancer and bone metastases; therefore, single-agent docetaxel should remain as one of the standard treatments. Funded: National Cancer Institute, Sanofi-Aventis, and Abbott Laboratories.
AB - Background: The endothelin pathway has a role in bone metastases, which are characteristic of advanced prostate cancer. Atrasentan, an endothelin receptor antagonist, has shown activity in prostate cancer. We therefore assessed its effect on survival in patients with castration-resistant prostate cancer with bone metastases. Methods: In a double-blind phase 3 trial, men with metastatic castration-resistant prostate cancer, stratified for progression type (prostate-specific antigen or radiological), baseline pain, extraskeletal metastases, and bisphosphonate use, were randomly assigned in a 1:1 ratio to docetaxel (75 mg/m2 every 21 days, intravenously) with atrasentan (10 mg/day, orally) or placebo for up to 12 cycles and treated until disease progression or unacceptable toxicity. Patients who did not progress on treatment were permitted to continue atrasentan or placebo for up to 52 weeks. Coprimary endpoints were progression-free survival (PFS) and overall survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00134056. Findings: 498 patients were randomly assigned to the atrasentan group and 496 to the placebo group. The trial was halted early for futility in April, 2011, after a planned interim analysis. Median PFS was 9·2 months (95% CI 8·5-9·9) in the atrasentan group and 9·1 months (8·4-10·2) in the placebo group (hazard ratio 1·02, 0·89-1·16; p=0·81). Median overall survival was 17·8 months (16·4-19·8) in the atrasentan group versus 17·6 months (16·4-20·1) in the placebo group (1·04, 0·90-1·19; p=0·64). 278 (57%) of 492 patients in the atrasentan group had grade 3 and greater toxicity compared with 294 (60%) of 486 in the placebo group (p=0·22). Three deaths in the atrasentan group and seven in the placebo group were judged to be possibly or probably due to protocol treatment. Interpretation: Atrasentan, when added to docetaxel, does not improve overall survival or PFS in men with castration-resistant prostate cancer and bone metastases; therefore, single-agent docetaxel should remain as one of the standard treatments. Funded: National Cancer Institute, Sanofi-Aventis, and Abbott Laboratories.
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U2 - 10.1016/S1470-2045(13)70294-8
DO - 10.1016/S1470-2045(13)70294-8
M3 - Article
C2 - 23871417
AN - SCOPUS:84880772151
SN - 1470-2045
VL - 14
SP - 893
EP - 900
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 9
ER -