Phase 1/2 Update: Concurrent Enzalutamide–Cabazitaxel Produces Durable PFS Signal in mCRPC

The updated Phase 1/2 data for concurrent enzalutamide plus cabazitaxel in chemo‑naïve mCRPC show deep biochemical responses and a promising signal for progression‑free outcomes, but the dataset remains hypothesis‑generating.

In a multi‑institutional single‑arm trial of enzalutamide with cabazitaxel (plus prednisone), 35 patients were included in the efficacy analysis with a median follow‑up of 23.7 months; 61.1% of patients achieved a ≥90% PSA decline (PSA90) (95% CI 43.5–76.9) and about 80% achieved PSA50.
Median PSA‑progression‑free survival was 11.9 months (95% CI 9.2–15.4), median radiographic PFS was 22.2 months (95% CI 13.6–25.2), and median overall survival was 25.1 months (95% CI 19.4–37.6) in the reported analysis.

Among 28 radiographically evaluable patients the objective response rate was 50% (14/28), including three complete responses and eleven partial responses.
Pharmacokinetic testing within the study detected a drug–drug interaction: enzalutamide co‑administration reduced cabazitaxel exposure (notable reductions in Cmax/AUC), which has implications for dosing and scheduling if this approach is tested further. Safety events were consistent with known profiles of each agent; the presentation with hematologic and non‑hematologic adverse events without a clear new synergistic toxicity signal.

Because the trial is single‑arm, small, and used PSA90 as its primary efficacy metric, cross‑trial comparisons are limited and these results should be viewed as hypothesis‑generating rather than practice‑changing; a randomized comparison versus standard sequential therapy (ARSI then taxane) is needed to demonstrate whether the deeper PSA responses and PFS signal translate into durable clinical benefit and survival advantage.

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