A phase I/II trial of concurrent chemo-hormonal enzalutamide and cabazitaxel in patients with metastatic castration-resistant prostate cancer

BACKGROUND AND OBJECTIVE: Despite treatment advances, treatment resistance for metastatic castration-resistant prostate cancer (mCRPC) is nearly universal. We studied the efficacy, safety, and pharmacokinetic properties of the combination of enzalutamide and cabazitaxel in patients with mCRPC. For phase 1, we examined the safety of combination therapy and determined the recommended phase 2 dose. Phase 2 primary endpoint included the percentage of patients achieving a ≥ 90% PSA decline (PSA90) as a measure of response to therapy. METHODS: A phase 1/2 single-arm, multi-institutional clinical trial enrolled adults with histologically confirmed progressive mCRPC without prior docetaxel or cabazitaxel chemotherapy for mCRPC. Co-administration of enzalutamide 160 mg orally once daily, cabazitaxel 25 mg/m2 IV once every 21 days, and prednisone 5 mg orally twice daily in mCRPC. Descriptive statistical analysis was used for all primary and secondary endpoints. Estimated proportions are with 95% confidence interval using the exact method. KEY FINDINGS: The study met its primary endpoint with 61.1% (95% CI, 43.5% to 76.9%) of patients achieving PSA90. Observed toxicities were similar to those seen with either agent alone. CONCLUSIONS: The combination of enzalutamide and cabazitaxel exhibited robust activity with tolerable side effects. Chemo-hormonal therapies warrant further study in mCRPC. WHAT DOES THE STUDY ADD: This study of enzalutamide and cabazitaxel combination therapy in patients with advanced, pre-treated mCRPC showed promising efficacy, indicating strong rationale for further investigation. PATIENT SUMMARY: In this report we looked at outcomes for patients with metastatic prostate cancer treated at multiple institutions with enzalutamide and cabazitaxel at the same time after castration therapy alone had stopped working. We found the combination was safe and had anti-cancer effect, warranting further investigation.