ARAMIS: trial | Bending the Curve: Trial by Trial

ARAMIS

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer

Phase 3N = 1,509NCT02200614

Population

Men with nonmetastatic castration-resistant prostate cancer and PSA doubling time of 10 months or less

Design

Randomized, double-blind, placebo-controlled phase 3 trial, 2:1 randomization to darolutamide 600 mg twice 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, with metastasis determined by independent central review of imaging every 16 weeks.

Primary endpoint

MFS

Arms

Placebo plus ADT (control, n = 554): Placebo plus continued ADT
Darolutamide plus ADT (experimental, n = 955): Darolutamide 600 mg twice daily plus continued ADT

People

Fizazi K, ARAMIS

MFSHR 0.41 (95% CI 0.34–0.50)Δ median MFS+22 monthsOSHR 0.69 (95% CI 0.53–0.88)Δ 36-month OS+6 points

Show the numbers

Results reported for ARAMIS
Endpoint	Analysis	Darolutamide plus ADT	Placebo plus ADT	Effect
MFSRandomized men (analysis population not stated in the abstract)	primaryFizazi 2019	median 40.4 months	median 18.4 months	HR 0.41 (95% CI 0.34–0.50)P<0.001Planned primary analysis after 437 primary end-point events. Hazard ratio for metastasis or death.
OSRandomized men (analysis population not stated in the abstract)	finalmedian follow-up 29 monthsFizazi 2020	83% at 3 y (80–86%)	77% at 3 y (72–81%)	HR 0.69 (95% CI 0.53–0.88)P=0.003Prespecified final analysis planned at about 240 deaths. All 170 patients still receiving placebo at unblinding crossed over to darolutamide. Landmarks are overall survival at 3 years.

Results reported for ARAMIS
Endpoint	Analysis	Darolutamide plus ADT	Placebo plus ADT	Effect
MFSRandomized men (analysis population not stated in the abstract)	primaryFizazi 2019	median 40.4 months	median 18.4 months	HR 0.41 (95% CI 0.34–0.50)P<0.001Planned primary analysis after 437 primary end-point events. Hazard ratio for metastasis or death.
OSRandomized men (analysis population not stated in the abstract)	finalmedian follow-up 29 monthsFizazi 2020	83% at 3 y (80–86%)	77% at 3 y (72–81%)	HR 0.69 (95% CI 0.53–0.88)P=0.003Prespecified final analysis planned at about 240 deaths. All 170 patients still receiving placebo at unblinding crossed over to darolutamide. Landmarks are overall survival at 3 years.

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

Data table

Endpoint	HR	95% CI
MFS	0.41	0.34–0.5
OS	0.69	0.53–0.88

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

Show curves

Placebo plus ADT (control)
Darolutamide 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	Darolutamide plus ADT
0	100.0%	100.0%
25	39.0%	65.1%
51	14.6%	41.7%
76	5.7%	27.1%
101	2.2%	17.7%

Appears in

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

Sources

Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2019;380(13):1235-1246.
PubMed DOI
Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020;383(11):1040-1049.
PubMed DOI