Table 1.

Objectives and endpoints

Primary objective	Primary endpoint
To evaluate the efficacy of enzalutamide plus LHRHa vs placebo plus LHRHa in patients with high-risk nmCSPC	MFS between enzalutamide plus LHRHa vs LHRHa
Key secondary objectives	Secondary endpoints
To evaluate efficacy of enzalutamide monotherapy vs placebo plus LHRHa	MFS between enzalutamide monotherapy vs placebo plus LHRHa
To compare enzalutamide plus LHRHa and enzalutamide alone vs placebo plus LHRHa in improving other efficacy measures	Time to PSA progression
	Time to first use of antineoplastic therapy
	Overall survival
Other secondary objectives	Other secondary endpoints
To compare enzalutamide plus LHRHa and enzalutamide alone vs placebo plus LHRHa in improving other efficacy measures	Time to distant metastasis
	Time to castration resistance
	Time to symptomatic progression
	Time to first symptomatic skeletal event (using the BPI-SF)
	Time to clinically relevant pain
To compare enzalutamide plus LHRHa and enzalutamide alone vs placebo plus LHRHa based on PSA at week 36 (ie, whereby treatment is suspended at week 37 in participants with undetectable levels of ≤0.2 ng/mL)	Proportion of participants per group who remain treatment-free 2 years after suspension of study drug treatment at week 37 due to undetectable PSA
	Proportion of participants per group with undetectable PSA 2 years after suspension of study drug treatment at week 37 due to undetectable PSA
	Proportion of participants per group with undetectable PSA at 36 weeks on study drug
	Time to resumption of any hormonal therapy following suspension at week 37 due to undetectable PSA
To compare PROs in enzalutamide plus LHRHa and enzalutamide alone arms vs placebo plus LHRHa arm	PROs as measured by FACT-P, EQ-5D-5L and EORTC QLQ-PR25
To compare overall safety in enzalutamide plus LHRHa and enzalutamide alone arms vs placebo plus LHRHa arm	Safety (adverse events, clinical laboratory tests, physical examinations and vital signs); monitored by independent data monitoring committee
Exploratory objective	Exploratory endpoint
To compare progression-free survival after first subsequent therapy	Time from the date of randomisation to the first occurrence of investigator-determined disease progression

BPI-SF, Brief Pain Inventory-Short Form; EQ-5D-5L, EuroQol 5-Dimension 5-Level Health Assessment Instrument; FACT-P, Functional Assessment of Cancer Therapy-Prostate; LHRHa, luteinising hormone-releasing hormone agonist; MFS, metastasis-free survival; nmCSPC, non-metastatic castration-sensitive prostate cancer; PROs, patient-reported outcomes; PSA, prostate-specific antigen; EORTC QLQ-PR25, EORTC Quality of Life Questionnaire-Prostate 25.