Androgen Receptor Gene Alterations and mCRPC Treatment Outcomes

Investigators assessed the impact of androgen receptor (AR) gene alterations in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line treatment with AR-targeted agents (ARATs). Lead author of the study, Nishita Tripathi, reported that patients with mCRPC who had AR alterations in circulating tumor DNA (ctDNA) had worse outcomes compared with patients with wild-type AR status. The data were presented at the ESMO Congress 2022.

The retrospective study enrolled 138 ARAT-naïve patients with confirmed mCRPC receiving first-line therapy with abiraterone or enzalutamide. Patients were categorized based on wild-type or alteration positive (AR+). Further analyses were performed based on type of alteration: amplification, mutation, or both.

Among all patients, 69 had wild-type and 69 had AR+ (amplification, n=40; mutation, n=17; both, n=12). Over a median follow-up of 44.3 months (interquartile range, 38.8-70.4), median progression-free survival was 12 months for AR wild-type, as compared with:

• 7 months for AR+ (hazard ratio [HR], 0.66; 95% CI, 0.46-0.94; P=.02),
• 8 months for amplification (HR, 0.64; 95% CI, 0.42-0.97; P=.04),
• 6 months for mutation (HR, 0.83; 95% CI, 0.47-1.47; P=.53)

Median overall survival was 53 months for wild-type, as compared with:

• 27 months for AR+ (HR, 0.42; 95% CI, 0.27-0.66; P>.01)
• 27 months for amplification (HR, 0.35; 95% CI, 0.21-0.59; P>.01)
• 35 months for mutation (HR, 0.49; 95% CI, 0.26-0.93; P=.03)

Overall, patients with mCRPC with AR alterations in ctDNA exhibited worse survival outcomes compared with patients with wild-type AR. Tripathi and colleagues suggested their findings “may aid in patient counseling, prognostication, and treatment decision.”

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