The final overall survival (OS) results for 3 major trials in non-metastatic castration-resistant prostate cancer (nmCRPC) were presented: the ARAMIS (darolutamide versus placebo, n=1,509), SPARTAN (apalutamide versus placebo, n=1,207) and PROSPER (enzalutamide versus placebo, n=1,401) trials [1-3].
In total, 3 novel androgen receptor blockers for the treatment of nmCRPC have been studied in large randomized clinical trials: apalutamide, enzalutamide, and darolutamide. Each treatment is effective and safe, but no head-to-head randomized nmCRPC trials have directly compared these treatments in assessing patient risk-benefit concerns.
ARAMIS was presented by Prof. Karim Fizazi (Institut Gustave Roussy, France) . With a median follow-up of approximately 29 months, the 3-year OS rates were 83% and 77% on the darolutamide and placebo arms, respectively (HR 0.69; 95% CI 0.53-0.88; P=0.003). Notably, darolutamide significantly delayed time to pain progression, with a median 40.3 months versus 25.4 months with placebo (HR 0.65; 95% CI 0.53-0.79; P<0.001). Darolutamide also significantly delayed the time to first cytotoxic chemotherapy and time to first symptomatic skeletal event (SSE) versus placebo.
Next, Prof. Eric Jay Small (UCSF Helen Diller Family Comprehensive Cancer Center, USA) presented the final results from SPARTAN . Median follow-up at the time of data cut-off was 52 months. Median OS was significantly longer among men receiving apalutamide than placebo (73.9 vs 59.9 months), corresponding to a relative reduction of 21.6% in the risk of death (HR 0.78; P=0.0161).
Finally, Prof. Cora Sternberg (Weill Cornell Medicine, USA) presented the final results of PROSPER . Median OS was 67.0 months in the enzalutamide group and 56.3 months in the placebo group (HR 0.73; 95% CI 0.61–0.89; P=0.001). An unplanned analysis indicated a 3-year OS of 80% versus 73%. The benefit of enzalutamide was generally consistent across prespecified subgroups, with the potential exception of the small group of patients receiving bone-sparing agents.
The safety profile of all 3 agents was consistent with prior analyses of the androgen receptor inhibitors. Moreover, the incidence of treatment-associated adverse events, including fatigue, bone fracture, decreased weight, rash, hypertension, and hot flash were not found to be statistically different between the agents.
1. Fizazi, K et al. Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for nonmetastatic castration-resistant prostate cancer (nmCRPC). ASCO Virtual Meeting, 29-31 May 2020, Abstract 5514.
2. Small EJ, et al. Final survival results from SPARTAN, a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). ASCO Virtual Meeting, 29-31 May 2020, Abstract 5516.
3. Sternberg C, et al. Final overall survival (OS) from PROSPER: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).ASCO Virtual Meeting, 29-31 May 2020, Abstract 5515.