medwireNews: Nonmetastatic castration-resistant prostate cancer (CRPC) patients aged 80 years and older benefit from treatment with second-generation androgen receptor inhibitors (ARIs), suggests a pooled analysis of three trials.
As reported in The Lancet Oncology, the metastasis-free survival (MFS) and overall survival (OS) gain offered by ARIs over placebo was maintained in men aged at least 80 years.
“These results support the use of androgen receptor inhibitors in older men, despite some increased toxicity in this age group,” say Jaleh Fallah and colleagues from the Food and Drug Administration in Silver Spring, Maryland, USA.
The exploratory pooled analysis included the 4117 participants of the placebo-controlled PROSPER, SPARTAN, and ARAMIS trials that evaluated the second-generation ARIs enzalutamide, apalutamide, and darolutamide, respectively, in nonmetastatic CRPC patients with a prostate-specific antigen level of at least 2.0 µg/L and a doubling time of 10 months or less.
The median MFS time was 40 months with ARI treatment and 22 months with placebo among the 1023 patients aged at least 80 years, giving a significant adjusted hazard ratio (HR) for metastasis or death of 0.37 in favor of ARI use.
The respective median MFS durations in patients younger than 80 years of age were 41 and 16 months, with a significant adjusted HR of 0.31.
OS similarly significantly favored the ARIs over placebo in patients aged 80 years or older, at a median of 54 versus 49 months (adjusted HR=0.79), and younger patients, at a median of 74 versus 61 months (adjusted HR=0.69).
The study authors note that “[p]atients aged 80 years or older experienced higher rates of grade 3–4 adverse events, serious adverse events, falls, and fractures, regardless of treatment group.”
For instance, in the older group, grade 3 or worse adverse events occurred in 55% of men given an ARI and 41% of those given placebo, while the corresponding rates in the younger group were 44% and 30%.
Similarly, any-grade falls were observed in 20% of ARI-treated older patients and 13% of younger patients, with respective rates in the placebo arm of 10% and 5%.
Fallah and colleagues also present data on patient-reported outcomes (PROs) evaluated using the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire. Among the 3651 participants who completed a PRO assessment at baseline and the 16-week mark, the total scores were comparable between age and treatment groups at both timepoints.
“There was [also] no marked difference from baseline in any of the five individual items from FACT-P across the age groups and treatment groups at week 16,” say the researchers, but they draw attention to the limitations of the PRO analysis, “including of the possibility that week 16 was not the optimal analysis timepoint given the duration of these trials.”
The investigators believe that these results “are important in clinical decision making, particularly for men aged older than 80 years, for whom there is little information in each product label regarding the risks and benefits of treatment with androgen receptor inhibitors.”
But highlighting the differences between patients enrolled in clinical trials and those seen in routine practice, they point out that “the interpretation of the safety and efficacy data in this exploratory pooled analysis and the generalisation of the results to patients in the real world needs to be done with caution and by taking the characteristics of the enrolled patients into account.”
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