Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer: Implications for prior therapy in clinical trials
Urologic Oncology: Seminars and Original Investigations,  Clinical Article

Pond GR et al. – In this hypothesis–generating analysis, patients treated with docetaxel–based chemotherapy following prior ketoconazole (KC) had numerically and consistently worse outcomes than patients not exposed to prior KC. Although the estimated differences did not attain statistical significance, evaluation of outcomes with docetaxel in particular, and all classes of novel and emerging agents following Abiraterone acetate, is of clinical importance, given its more potent androgen synthesis inhibition compared with KC. Drug development should take into account the potential impact of previous therapy.

Methods
  • A randomized phase II trial of men with mCRPC treated with DP + AT–101 (bcl–2 inhibitor) vs. DP plus placebo was analyzed.
  • Both arms were combined for analysis as no significant differences were seen.
  • Overall survival (OS), progression–free survival (PFS), objective response (ORR), pain, and prostate–specific antigen (PSA) response rates were estimated with and without prior KC.
  • Cox proportional hazards regression models were used to estimate the effect of covariates on OS.

Results
  • Of 220 evaluable men, 40 (18.2%) received prior KC. The median OS with DP–based therapy of KC–naive patients (18.3 months, 95% CI: 15.0, 24.5) and post–KC patients (17.0 months, 95% CI: 9.9, 20.4) was not statistically different (P = 0.20).
  • After controlling for prognostic classifications, analyses demonstrated consistent trends for worsening of OS after KC, with (hazard ratios (HRs) 1.33–1.46.
  • Similar unfavorable trends were observed for ORR, PSA declines, and PFS.

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