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BACKGROUND: Preliminary 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. METHODS: In CALGB trial 90401, 1050 men with chemotherapy-naive mCRPC were randomized to receive treatment with docetaxel and predni-sone 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. RESULTS: Baseline 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, respec-tively; stratified log-rank P = .635), PFS (median PFS, 8.1 months vs 8.6 months, respectively; stratified log-rank P = .342), the propor-tion 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). CONCLUSIONS: As 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 [ABSTRACT FROM AUTHOR]

ABSTRACTObjectives: To explore whether serum prostate specific antigen (PSA) decline can be used as a prognostic factor for survival among patients with androgen-independent prostate cancer (AIPC) who are treated with a secondary hormonal therapy, megestrol acetate. Materials and Methods: One hundred forty-nine patients were randomized with equal probability to either low-dose (160 mg/day) or high-dose (640 mg/day) megestrol acetate. Patients were stratified on performance status (0–1, or 2) and on disease measurability (measurable, or evaluable disease). Results: Patients with high pretreatment PSA (≥95 ng/ml) had worse survival times than patients with low PSA (<95), with a hazard ratio of 1.6 (p = 0.003). The median survival times for patients with a ≥50% reduction in PSA at 8 weeks and those patients without a 50% reduction were 15 and 11 months, respectively (p = 0.763). A landmark analysis at 8 weeks showed that a PSA decline was significantly associated with survival. The survival time for patients whose PSA dropped below the pretreatment levels (median = 15 months) were significantly longer than for patients who did not have a decline in PSA (median = 9 months, p = 0.031). Similar significant results were observed between PSA reduction and survival when landmark analyses were performed at 12 and 16 weeks. PSA changes during the first 45 days after the initiation of therapy were significantly related to survival. The median survival time for patients whose PSA doubled during the first 45 days after treatment and for patients whose PSA did not double during the first 45 days were 10 and 14 months, respectively (p = 0.020). Conclusions: PSA decline is significantly associated with longer survival times in prostate patients treated with secondary hormonal manipulation. Longer survival time is observed among the following AIPC patients: 1) those whose pretreatment PSA were <95 ng/ml: 2) those whose PSA decline was >0% from baseline; and... [ABSTRACT FROM AUTHOR]