PROSPER: trial | Bending the Curve: Trial by Trial

PROSPER

Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer

Phase 3N = 1,401NCT02003924

Population

Men with nonmetastatic castration-resistant prostate cancer and a rapidly rising PSA (median doubling time 3.7 months)

Design

Double-blind phase 3 trial, 2:1 randomization to enzalutamide 160 mg daily or placebo, all continuing ADT. Eligibility: nonmetastatic castration-resistant prostate cancer and PSA doubling time of 10 months or less. Primary end point metastasis-free survival (time from randomization to radiographic progression, or death without radiographic progression).

Primary endpoint

MFS

Arms

Placebo plus ADT (control, n = 468): Placebo plus continued ADT
Enzalutamide plus ADT (experimental, n = 933): Enzalutamide 160 mg daily plus continued ADT

People

Hussain M, PROSPER

MFSHR 0.29 (95% CI 0.24–0.35)Δ median MFS+21.9 monthsOSHR 0.73 (95% CI 0.61–0.89)Δ median OS+10.7 months

Show the numbers

Results reported for PROSPER
Endpoint	Analysis	Enzalutamide plus ADT	Placebo plus ADT	Effect
MFSRandomized men (analysis population not stated in the abstract)	primaryHussain 2018	median 36.6 months	median 14.7 months	HR 0.29 (95% CI 0.24–0.35)P<0.001Metastasis or death in 219 of 933 patients (23%) with enzalutamide and 228 of 468 (49%) with placebo. Hazard ratio for metastasis or death.
OSRandomized men (analysis population not stated in the abstract)	finalSternberg 2020	median 67 months	median 56.3 months (54.4–63.0)	HR 0.73 (95% CI 0.61–0.89)P=0.001288 of 933 (31%) deaths with enzalutamide and 178 of 468 (38%) with placebo. The 95% CI for the enzalutamide median is 64.0 to not reached.

Results reported for PROSPER
Endpoint	Analysis	Enzalutamide plus ADT	Placebo plus ADT	Effect
MFSRandomized men (analysis population not stated in the abstract)	primaryHussain 2018	median 36.6 months	median 14.7 months	HR 0.29 (95% CI 0.24–0.35)P<0.001Metastasis or death in 219 of 933 patients (23%) with enzalutamide and 228 of 468 (49%) with placebo. Hazard ratio for metastasis or death.
OSRandomized men (analysis population not stated in the abstract)	finalSternberg 2020	median 67 months	median 56.3 months (54.4–63.0)	HR 0.73 (95% CI 0.61–0.89)P=0.001288 of 933 (31%) deaths with enzalutamide and 178 of 468 (38%) with placebo. The 95% CI for the enzalutamide median is 64.0 to not reached.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
MFS	0.29	0.24–0.35
OS	0.73	0.61–0.89

Illustrative — modelled from reported values, not trial data. MFS, primary.

Show curves

Placebo plus ADT (control)
Enzalutamide plus ADT (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus ADT	Enzalutamide plus ADT
0	100.0%	100.0%
23	33.8%	64.7%
46	11.4%	41.8%
69	3.9%	27.1%
92	1.3%	17.5%

Illustrative — modelled from reported values, not trial data. OS, final.

Show curves

Placebo plus ADT (control)
Enzalutamide plus ADT (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Placebo plus ADT	Enzalutamide plus ADT
0	100.0%	100.0%
42	59.6%	64.8%
84	35.6%	41.9%
126	21.2%	27.2%
168	12.6%	17.6%

Appears in

2018 AR inhibitors and metastasis-free survival in non-metastatic CRPC

Sources

Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018;378(26):2465-2474.
PubMed DOI
Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, et al. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2020;382(23):2197-2206.
PubMed DOI