Metastatic hormone-sensitive prostate cancer: How should it be treated?

Table 2 Survival and toxicity results of the phase 3 randomized clinical trials of second-generation antihormonal treatments in metastatic hormone-sensitive prostate cancer

Trial	Follow-up in mo	Main results	Quality of life	Toxicity
LATITUDE	51.8	Reduced mortality risk by 34% with abiraterone (P < 0.001); OS at 3 yr (66% vs 49%); median OS (53.3 mo vs 36.5 mo). Reduction in risk of radiographic progression by 53% with abiraterone (P < 0.001) (33 mo vs 14.8 mo)	Abiraterone improved all QoL-related parameters	Toxicity grade 3-4: (1) Abiraterone: 63%; (2) Placebo: 48%. Treatment-related deaths: (1) Abiraterone: 5%; and (2) Placebo: 4%
STAMPEDE	40	Reduction in mortality risk of 39% with abiraterone (P < 0.001). Reduction in risk of progression of 69% with abiraterone (P < 0.001). Treatment benefit in all patients according to risk group and disease volume	-	Toxicity grade ≥ 3: (1) Abiraterone: 47%; and (2) ADT: 33%
ENZAMET	33	Reduction in mortality risk by 67% with enzalutamide (P = 0.002). 3-yr OS (82% vs 72%)	No SD	Toxicity grade ≥ 3: (1) Enzalutamide: 58%; and (2) AA: 43%
TITAN	22.7	Reduction in risk of radiographic progression or death by 52% with apalutamide (P < 0.001). 2-yr rPFS (68.2% vs 47.5%). Reduction in mortality risk of 33% with apalutamide (P = 0.005). 2-yr OS (82.4% vs 73.5%). Treatment benefit in all patients according to disease volume, significant in rPFS and OS in high-volume disease	No SD	Toxicity grade 3-4: (1) Apalutamide: 42.2%; and (2) Placebo: 40.8%. Treatment-related deaths: (1) Apalutamide: 1.9%; and (2) Placebo: 3%
ARCHES	14.4	Reduction in risk of radiographic progression or death of 61% with enzalutamide (P < 0.001) (NR vs 19 mo). OS (P = 0.336). Benefit in rPFS in both high and low volume disease	No SD	No SD. Treatment-related deaths: (1) Enzalutamide: 2.4%; and (2) Placebo: 1.7%

AA: First-generation antiandrogens; ADT: Androgen deprivation therapy; NR: Not reached; OS: Overall survival; QoL: Quality of life; rPFS: Radiographic progression-free survival; SD: Statistical differences.