b'and overall survival, they should be used with a full understanding of their risks, interactions and contraindications. Graff and Feng drilled down into the base studies to identify the ad-vantagesandpotentialchallengesinolder menofthethreenext-generationhormonal therapies approved by the U.S. Food and Drug Administration for treatment of nmCRPC. TheSPARTANtrialcomparedapalutamide to placebo. In men aged 75 and older, the drug increasedmetastasis-freesurvival59%and progression-freesurvival41%.Grade3or4 adverse events were common in both the inter-ventionandplaceboarmsinthisagegroup, 50.4% and 37.4%, respectively. The risk of falls was 18.9% in the apalutamide group and 13.4% in the placebogroup. Additional follow-up to theSPARTANstudyshowedmedianoverall survival benefit of 22%, though data for the old-est group was broken out.The PROSPER trial evaluated metastasis-free survival for enzalutamide compared to placebo. Overall, the next-generation androgen inhibitor reduced the risk of metastasis 71% compared to placebo, 36.6 months vs. 14.7 months. Median overallsurvivalwas67monthswithenzalu-tamide and 56.3 months with placebo. For men age 75 and older, the use of the drug reduced mortal- The researchers concluded that these three drugs ity risk 19%. As with previous trials, three patients inshared similar and significant efficacy, with [metas-PROSPER who received enzalutamide experiencedtasis-free survival] improvements of approximately seizures. Men in the treatment group also had highertwoyearsoverplaceboand[overallsurvival] risk of fatigue, hypertension and falls across all ageimprovement,bothofwhichremainedsignificant groups than men who received placebo. inthesubgroupage75andolder. Theyencour-TheARAMIStriallookeddarolutamideversusaged clinicians to consider the difference in adverse placebo. Among men aged 75 to 84 years, darolu- events, drug-drug interactions as well as drug avail-tamide reduced the risk of metastasis 57% comparedability when selecting a treatment for older men with with placebo. For those 85 and older, risk of metas- nonmetastatic CRPC. tasis declined 49%. Overall risk of death declined1Feng Z, Graff JN. Next-Generation Androgen Receptor-Signaling In-31% with darolutamide, but specifics by age grouphibitors for Prostate Cancer: Considerations for Older Patients. Drugs were not available. Patients with seizure were notAging. 2021 Feb;38(2):111-123. doi: 10.1007/s40266-020-00809-3. excluded from the ARAMIS trial because of the lowEpub 2021 Feb 9. PMID: 33559101.penetration of the blood-brain barrier by the drug,2Fallah J, Zhang L, Amatya A, Gong Y, et. al. Survival outcomes and 0.2% of patients in both arms experienced sei- in older men with non-metastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: a US Food and zures. Darolutamide was not associated with higherDrug Administration pooled analysis of patient-level data from risk of falls, fractures, fatigue, cognitive impairment three randomised trials. Lancet Oncol. 2021 Sep;22(9):1230-1239. orhypertensionthanplacebointhebroadpatientdoi: 10.1016/S1470-2045(21)00334-X. Epub 2021 Jul 23. PMID: population, though safety information on those age34310904.75 and older was not available.111'