OBJECTIVES: A targeted literature review was conducted to investigate the most recent emerging trends in biomarkers evaluated in metastatic castration resistant prostate cancer (mCRPC) clinical trials.

METHODS: Electronic databases (Embase, MEDLINE, Cochrane Library), ClinicalTrials.gov, and key English-language conference proceedings (2019 – 2022) were reviewed. Phase 1 or 2 trials of systemic treatments that utilized biomarker data in correlative analyses of pharmacokinetic, efficacy, and/or safety outcomes in mCRPC were included. Biomarker data was descriptively compared between trials published in two time periods (Period 1: 1/1/19 – 12/31/20, Period 2: 1/1/21 – 11/30/22).

RESULTS: A total of 55 trials were included (n=30 in Period 1, n=25 in Period 2). Androgen receptor (AR) aberrations were the most commonly reported among all biomarkers in both Periods (43% and 48%, respectively). Comparing Period 1 and 2, there was an increase in the use of biomarkers related to DNA damage and repair (DDR) deficiencies (30% to 48%, respectively), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway activation (17% to 32%, respectively), and tumor protein 53 (TP53) mutations (10% to 28%, respectively). Across all studies, biomarkers related to tumor mutational burden, microsatellite instability status, or immune markers were studied mostly in association with immune modulators. None of 55 trials correlated biomarkers to pharmacokinetic or safety outcomes, but 51% reported survival outcomes, which were primarily correlated to AR and DDR deficiencies. Of these, 64% quantified this association statistically.

CONCLUSIONS: While AR pathway biomarkers remained the most common in early mCRPC trials across both time periods, the use of DDR, PI3K/AKT, and TP53 biomarkers increased from Period 1 to 2. Survival outcomes correlated to AR and other biomarkers were also reported in over half of the early mCRPC trials.