Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: Post hoc analysis of study COU-AA-302 Journal Article
| Authors: | Saad, F.; Shore, N.; Van Poppel, H.; Rathkopf, D. E.; Smith, M. R.; de Bono, J. S.; Logothetis, C. J.; De Souza, P.; Fizazi, K.; Mulders, P. F. A.; Mainwaring, P.; Hainsworth, J. D.; Beer, T. M.; North, S.; Fradet, Y.; Griffin, T. A.; De Porre, P.; Londhe, A.; Kheoh, T.; Small, E. J.; Scher, H. I.; Molina, A.; Ryan, C. J. |
| Article Title: | Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: Post hoc analysis of study COU-AA-302 |
| Abstract: | Background Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. Objective Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. Design, setting, and participants This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Intervention Patients were grouped by concomitant BTT use or no BTT use. Outcome measurements and statistical analysis Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. Results and limitations While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p = 0.01) and increased the time to ECOG deterioration (HR 0.75; p < 0.001) and time to opiate use for cancer-related pain (HR 0.80; p = 0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients. Conclusions AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT. Patient summary Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone. Trial registration ClinicalTrials.gov NCT00887198. © 2015 European Association of Urology. |
| Keywords: | adult; aged; survival rate; major clinical study; overall survival; prednisone; drug safety; hypertension; monotherapy; follow up; edema; progression free survival; heart disease; alanine aminotransferase blood level; alanine aminotransferase; hypokalemia; abiraterone acetate; fluid retention; castration resistant prostate cancer; post hoc analysis; randomized controlled trial (topic); jaw osteonecrosis; chemotherapy-naive; metastatic castration-resistant prostate cancer; human; male; priority journal; article; metastatic castration resistant prostate cancer; bone-targeted therapy |
| Journal Title: | European Urology |
| Volume: | 68 |
| Issue: | 4 |
| ISSN: | 0302-2838 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2015-10-01 |
| Start Page: | 570 |
| End Page: | 577 |
| Language: | English |
| DOI: | 10.1016/j.eururo.2015.04.032 |
| PROVIDER: | scopus |
| PUBMED: | 25985882 |
| PMCID: | PMC5056561 |
| DOI/URL: | |
| Notes: | Export Date: 2 October 2015 -- Source: Scopus |
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