1. The effect of prior androgen synthesis inhibition on outcomes of subsequent therapy with docetaxel in patients with metastatic castrate‐resistant prostate cancer
- Author
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Aggarwal, Rahul, Halabi, Susan, Kelly, William Kevin, George, Daniel, Mahoney, John F, Millard, Frederick, Stadler, Walter M, Morris, Michael J, Kantoff, Philip, Monk, J Paul, Carducci, Michael, Small, Eric J, and Oncology, for the Alliance for Clinical Trials in
- Subjects
Prostate Cancer ,Clinical Research ,Urologic Diseases ,Clinical Trials and Supportive Activities ,Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Aged ,Androgen Antagonists ,Antibodies ,Monoclonal ,Humanized ,Antifungal Agents ,Antineoplastic Combined Chemotherapy Protocols ,Bevacizumab ,Bone Neoplasms ,Chemotherapy ,Adjuvant ,Disease Progression ,Docetaxel ,Drug Therapy ,Combination ,Follow-Up Studies ,Humans ,International Agencies ,Ketoconazole ,Liver Neoplasms ,Lung Neoplasms ,Lymphatic Metastasis ,Male ,Middle Aged ,Neoplasm Staging ,Orchiectomy ,Prednisone ,Prognosis ,Prostatic Neoplasms ,Retrospective Studies ,Survival Rate ,Taxoids ,prostatic neoplasms ,chemotherapy ,ketoconazole ,steroid 17-alpha-hydroxylase ,androgen antagonists ,Alliance for Clinical Trials in Oncology ,Oncology and Carcinogenesis ,Public Health and Health Services ,Oncology & Carcinogenesis - Abstract
BackgroundPreliminary data suggest a potential decreased benefit of docetaxel in patients with metastatic, castration-resistant prostate cancer (mCRPC) who previously received abiraterone acetate, a novel androgen synthesis inhibitor (ASI). Cancer and Leukemia Group B (CALGB) trial 90401 (Alliance), a phase 3 trial in patients with mCRPC who received docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes after docetaxel.MethodsIn CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and prednisone that included either bevacizumab or placebo. In total, 1005 men (96%) had data available regarding prior ketoconazole therapy. The observed effects of prior ketoconazole on overall survival (OS), progression-free survival (PFS), prostate-specific antigen (PSA) decline, and the objective response rate (ORR) were assessed using proportional hazards and Poisson regression methods adjusted for validated prognostic factors and treatment arm.ResultsBaseline characteristics between patients who did (N=277) and did not (N=728) receive prior ketoconazole therapy were similar. There were no statistically significant differences between patients who did and those who did not receive prior ketoconazole therapy with respect to OS (median OS, 21.1 months vs 22.3 months, respectively; stratified log-rank P=.635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P=.342), the proportion achieving a decline ≥ 50% in PSA (61% vs 66%, respectively; relative risk, 1.09; adjusted P=.129), or ORR (39% vs 43%, respectively; relative risk, 1.11; adjusted P=.366).ConclusionsAs measured by OS, PFS, PSA, and the ORR, there was no evidence that prior treatment with ketoconazole had an impact on the clinical outcomes of patients with mCRPC who received subsequent docetaxel-based therapy. The current results highlight the need for prospective studies to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC.
- Published
- 2013