Darolutamide Maintenance in Patients With Metastatic Castration-Resistant Prostate Cancer With Nonprogressive Disease After Taxane Treatment (SAKK 08/16)

Purpose: To assess the efficacy and safety of darolutamide maintenance after successful taxane chemotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and methods: Swiss Group for Clinical Cancer Research (SAKK) 08/16 is a randomized phase II study. Patients with mCRPC who received prior androgen-receptor pathway inhibitors (ARPIs) and subsequently had nonprogressive disease on a taxane were randomly assigned to darolutamide 600 mg twice a day or placebo twice a day. The primary end point was radiographic progression-free survival (rPFS) at 12 weeks. Secondary end points were rPFS, event-free survival, overall survival (OS), prostate-specific antigen (PSA) 50% response rate, and adverse events. Results: Overall, 92 patients were recruited by 26 centers. Prior taxane was docetaxel in 93% and cabazitaxel in 7%. Prior ARPI was abiraterone in 60%, enzalutamide in 31%, and both in 9%. rPFS at 12 weeks was significantly improved with darolutamide (64.7% v 52.2%; P = .127). Median rPFS on darolutamide was 5.5 versus 4.5 months on placebo (hazard ratio [HR], 0.54; 95% CI, 0.32 to 0.91; P = .017), and median event-free survival was 5.4 versus 2.9 months (HR, 0.46; 95% CI, 0.29 to 0.73; P = .001). PSA 50% response rate was improved (22% v 4%; P = .014). Median OS for darolutamide was 24 versus 21.3 months for placebo (HR, 0.62; 95% CI, 0.3 to 1.26; P = .181). Treatment-related adverse events were similar in both arms. Conclusion: SAKK 08/16 met its primary end point, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one ARPI resulted in a statistically significant but clinically modest rPFS prolongation with good tolerability. The median OS with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with mCRPC, especially those who responded well to prior ARPI.