Enzalutamide and Docetaxel in Combination With Androgen Deprivation for Men With Metastatic Hormone-Sensitive...

Androgen receptor pathway inhibitors (ARPI) in combination with docetaxel (Doc) and androgen deprivation therapy (ADT) has improved outcomes for men with metastatic hormone sensitive prostate cancer (mHSPC). We hypothesized that combining ADT with Doc and enzalutamide (Enz) would improve the 52-week prostate-specific antigen (PSA) complete response (CR) rate compared to a historical control with ADT + Doc.

In a single arm phase II trial, treatment-naïve patients with mHSPC received ADT + Doc every 3 weeks up to 6 cycles and Enz daily until progression. The primary endpoint was 52-week PSA CR. Secondary endpoints included safety/toxicity, best PSA response, time to castration resistance and overall survival (OS).

Between Sep 2017 and Aug 2021, 40 patients were enrolled and 36 evaluable for the primary endpoint. At data cutoff, median follow up was 56.1 months. Thirty patients (75%) had high-volume disease. Median age was 64.5 years. Median pretreatment PSA was 129.5ng/ml. 52-week PSA CR occurred in 22/36 (61.1%) patients compared to historical control (P < .001). Median OS was not reached. Patients who did not achieve a 52-week PSA CR had shorter OS (HR, 4.67; 95% CI 1.41-15.55; P = .006). Treatment-related Grade 3 to 5 adverse events occurred in 17/40 (42.5%) patients.

ADT+Doc+Enz improved 52-week PSA CR compared to historical control with ADT+Doc. Achieving a PSA CR after 1 year of therapy correlated with improved OS. These results are consistent with recent phase III studies and support using triplet regimens that combine ADT+Doc+ARPI for newly diagnosed mHSPC.