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Update further details darolutamide efficacy in nmCRPC

Alicia Morgans, MD, MPH

Alicia Morgans, MD, MPH

A post-hoc analysis of the phase 3 ARAMIS trial provided additional efficacy evidence for darolutamide (Nubeqa) in nonmetastatic castration-resistant prostate cancer (CRPC), including benefits related to prostate cancer–specific survival and reaching a PSA level <0.2 ng/mL.1

The double-blind ARAMIS trial included 1509 patients with nonmetastatic CRPC. Patients were randomized in a 2:1 ratio to receive oral darolutamide at 600 mg twice daily plus androgen deprivation therapy (ADT; n = 955) or placebo plus ADT (n = 554). Previously reported data from the trial showed that darolutamide significantly extended metastasis-free survival (MFS) and overall survival (OS) versus placebo.

The ARAMIS OS data showed that the addition of darolutamide reduced the risk of death by 31% vs ADT alone in this patient population (HR, 0.69; 95% CI, 0.53-0.88; P = .003).2 Findings from the post hoc analysis shared during the 2024 ASCO Annual Meeting by Alicia Morgans MD, MPH, showed that at 30 months’ follow-up, darolutamide specifically reduced the incidence of prostate cancer–related deaths, which occurred in 6% of the darolutamide arm vs 8.2% of the placebo arm.1

Morgans, an associate professor of medicine, Harvard Medical School, and medical director, Survivorship Program, Dana-Farber Cancer Institute, further explained that “Fewer patients receiving darolutamide vs placebo had PSA progression alone (7.8% vs 35.9%) or both PSA and radiological progression (5.4% vs 21.4%) at 12 months.”

In patients with a PSA ≥0.2 ng/mL, those treated with placebo compared with darolutamide had higher PSA levels at the time of radiological progression, at 3.7 vs 2.4 ng/mL, respectively.

PSA responses were deep and durable with darolutamide. There was a 50-fold greater chance of reaching PSA <0.2 ng/mL with darolutamide vs placebo, at a rate of 25.1% vs 0.5%, respectively. Across all patients enrolled in ARAMIS, time to PSA progression was 33.2 months vs 7.3 months with darolutamide vs placebo, respectively (HR, 0.13; 95% CI, 0.11-0.16).

“At 24 months, patients receiving darolutamide who had a PSA level <0.2 ng/mL had a lower risk of radiological progression vs patients with a PSA level ≥0.2 ng/mL, at 8.7% vs 33%,” said Morgans. “At 36 months, the cumulative incidence of radiological progression remained at 8.7% for darolutamide patients with PSA <0.2 ng/mL and increased to 50% in patients with PSA ≥0.2 ng/mL.”

Morgans explained that no specific outcome patterns emerged for the 11 patients who had a PSA level <0.2 ng/mL and radiological progression. For these patients PSA levels at the time of radiological progression ranged from 0.02 ng/mL to 438.46 ng/mL and the time to radiological progression ranged from 4 to 22 months.

In her concluding remarks, Morgans said, “Further research is needed on the association between low PSA values (<0.2 ng/mL) and radiological progression.”

Darolutamide was approved for use in this setting by the FDA in July 2019 based on primary data from ARAMIS, which showed that in the overall population the median MFS was 40.4 months in the darolutamide cohort and 18.4 months in the placebo cohort, translating to a 59% reduction in the risk of metastases or death (HR, 0.41; 95% CI, 0.34-0.50; P <.001).3 The FDA subsequently approved a label update for this indication to include the OS data from the ARAMIS trial.4


1. Morgans AK, Sweeney C, Wallis CJD, et al. Association between prostate-specific antigen (PSA) level <0.2 ng/mL and risk of radiological progression in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Follow-up analysis of ARAMIS. J Clin Oncol 42, 2024 (suppl 16; abstr 5022). doi: 10.1200/JCO.2024.42.16_suppl.5022

2. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. doi: 10.1056/NEJMoa2001342

3. FDA approves darolutamide for non-metastatic castration-resistant prostate cancer. Published online July 30, 2019. Accessed June 2, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-non-metastatic-castration-resistant-prostate-cancer

4. U.S. FDA Approves Addition of Overall Survival and Other Secondary Endpoint Data to NUBEQA® (darolutamide) Prescribing Information. Posted online January 8, 2021. https://bit.ly/2L60YfW. Accessed January 8, 2021.

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