Androgen Receptor Inhibitors May Offer Benefit in Geriatric Non-Metastatic Castration-Resistant Prostate Cancer

A pooled analysis of patient-level data regarding 3 randomized trials, including the phase 3 SPARTAN (NCT01946204), PROSPER (NCT02003924), and ARAMIS trials (NCT02200614), supports the use of androgen receptor inhibitors in the treatment geriatric patient with non-metastatic castration-resistant prostate cancer.

The survival analyses for patients aged 80 years or older treated with androgen receptor inhibitors identified an estimated median metastasis-free survival of 40 months (95% CI, 36-41) compared with 22 months (95% CI, 18-29) for patients in the placebo groups (adjusted hazard ratio [HR], 0.37; 95% CI, 0.28-0.47). Additionally, the median overall survival (OS) was 54 months (95% CI, 50-61) and 49 months (95% CI, 43-58) for older patients treated with androgen receptor inhibitors and those in the placebo groups, respectively (adjusted HR, 0.79; 95%, CI, 0.64-0.98).

“The findings of this pooled analysis support the use of androgen receptor inhibitors in older patients with non-metastatic castration-resistant prostate cancer. Incorporating geriatric assessment tools in the care of older adults with prostate cancer might help clinicians to offer [individualized] treatment to each patient, on the basis of the patient’s health status, and the drug’s safety and efficacy profile,” the investigators wrote.

Between October 14, 2013, and March 9, 2018, 4117 patients were randomly assigned to receive either an androgen receptor inhibitor (n = 2694), or placebo groups (n = 1423) who met the inclusion criteria for this pooled analysis. The analysis included the SPARTAN trial, which examined the use of apalutamide (Erleada) in men with nmCRPC; the PROSPER trial, examining the safety and efficacy of enzalutamide (Xtandi) in patients with nmCRPC; and the ARAMIS trial assessing darolutamide (Nubeqa) in those with high-risk nmCRPC.

Patients were eligible to enroll in each of the 3 trials if they were 18 years or older with an ECOG performance score of 0 to 1 and non-metastatic castration-resistant prostate cancer. The patients who were randomized to either androgen receptor inhibitor treatment or placebo were eligible for survival assessment. Patients who received at least 1 dose of treatment were evaluated for the safety analysis.

At the time of enrollment, median age was 74 years (range, 48-97). The median follow-up for duration of metastasis-free survival (MFS) was 18 months (IQR, 11-26) and 44 months (IQR, 32-55) for OS.

For patients younger than 80 years, the estimated median MFS was 41 months (95% CI, 36–not estimable [NE]) for patients in the androgen receptor inhibitor groups and 16 months (95% CI, 15-18) for patients in the placebo groups (adjusted HR, 0.31; 95% CI, 0.27-0.35). The median OS was 74 months (95% CI, 74-NE) vs 61 months (95% CI, 56-NE) for patients in the androgen receptor inhibitor groups and placebo groups, respectively (adjusted HR, 0.69; 95% CI, 0.60-0.80).

Among patients in the androgen receptor inhibitor groups who were aged 80 years or older, 55% experienced grade 3 or higher adverse effects (AEs) compared with 41% of patients in the placebo groups. For patients younger than 80 years, grade 3 or worse AEs were observed in 44% and 30% of patients in the androgen receptor inhibitor and placebo groups, respectively.

The most common grade 3/4 AEs were hypertension and fracture. For patients 80 years or older in the androgen receptor inhibitor groups, hypertension was observed in 8% of patients aged 80 years or older and 8% of patients younger than 80 years vs 6% of patients aged 80 years or older and 5% of patients younger than 80 years in the placebo groups. Fracture in the androgen receptor inhibitor groups was observed in 5% and 3% of patients vs the placebo groups at 3% and 1% of patients 80 years or older and younger than 80 years, respectively.

Reference

Fallah J, Zhang L, Amatya A, et al. Survival outcomes in older men with non-metastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: a US Food and Drug Administration pooled analysis of patient-level data from three randomised trials. Lancet Oncol. Published online ahead of print, July 23, 2021. doi:10.1016/S1470-2045(21)00334-X