Silver Spring, MD—Are second-generation androgen-receptor inhibitors effective and safe in men aged 80 years or older with nonmetastatic castration-resistant prostate cancer?
An FDA study determined the benefit-risk profile of those medications. Results were published in the Lancet Oncology.
Researchers searched for all randomized, controlled clinical trials evaluating second-generation androgen-receptor inhibitors in patients with nonmetastatic castration-resistant prostate cancer submitted to the FDA before August 15, 2020; data from the three trials that met the selection criteria were pooled. All three enrolled patients who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–1, castration-resistant prostate cancer, prostate-specific antigen (PSA) 2·0 μg/L or greater, PSA doubling time of 10 months or less, and no evidence of distant metastatic disease on conventional imaging per the investigator’s assessment at the time of screening.
In addition, all the patients in those studies had histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small-cell features. The FDA study team evaluated the effect of age on metastasis-free survival and overall survival across age groups, comparing men younger than 80 with those 80 or older in the intention-to-treat population. Patients who received at least one dose of study treatment were included in safety analyses.
Between October 14, 2013, and March 9, 2018, 4,117 patients were assigned to androgen-receptor inhibitor treatment—with apalutamide, enzalutamide, or daralutamide—or placebo across three randomized trials. In those studies, the median follow-up duration for metastasis-free survival was 18 months (IQR 11.26) and for overall survival was 44 months (32-55).
Results indicated that, in 1,023 patients aged 80 years or older, the estimated median metastasis-free survival was 40 months (95% CI, 36-41) in the androgen-receptor inhibitor groups and 22 months (18-29) in the placebo groups (adjusted hazard ratio [HR] 0.37 [95% CI, 0·28-0·47]). At the same time, median overall survival was 54 months (50-61) versus 49 months (43-58), respectively (adjusted HR 0.79 [0·64-0·98]).
For 3,094 patients younger than age 80 years, the estimated median metastasis-free survival was 41 months (95% CI, 36-not estimable [NE]) in the androgen-receptor inhibitor groups and 16 months (15-18) in the placebo groups (adjusted HR 0.31 [95% CI, 0.27-0·35]). Their median overall survival time was 74 months (74-NE) versus 61 months (56-NE), respectively (adjusted HR 0.69 [0·60-0·80]).
Researchers point out that, in 55% of patients aged 80 years or older in the androgen-receptor inhibitor groups, grade 3 or worse adverse events were reported. Adverse events were reported in 41% of 344 over-80 patients in the placebo groups, compared with, among patients younger than age 80 years, 44% of 2015 patients in the androgen-receptor inhibitor groups, and 30% of 1,073 patients in the placebo groups.
The most common grade 3-4 adverse events were:
• Hypertension (8% of patients younger than age 80 years and 8% aged 80 years and older in the androgen-receptor inhibitor groups vs. 5% younger than age 80 years and 6% aged 80 years and older in the placebo groups), and
• Fracture (3% and 5% in the androgen-receptor inhibitor groups vs. 1% and 3% in the placebo groups, respectively).
“The findings of this pooled analysis support the use of androgen receptor inhibitors in older men with non-metastatic castration-resistant prostate cancer,” the researchers conclude. “Incorporating geriatric assessment tools in the care of older adults with non-metastatic castration-resistant prostate cancer might help clinicians to offer individualized treatment to each patient.”
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