Potential Predictive Biomarkers for PSMA-Targeted Therapies in Prostate Cancer
Posted: Wednesday, July 31, 2019
Research findings presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5002) reported that prostate-specific membrane antigen (PSMA) in patients diagnosed with castration-resistant or castration-specific prostate cancer exhibit “intra- and interpatient heterogeneity. “We show for the first time that [DNA damage repair] gene aberrations [are] associated with high [membranous] PSMA expression and may serve as predictive biomarkers for PSMA-targeted therapies,” Johann S. de Bono, PhD, of The Royal Marsden National Health Service Foundation Trust, London, and colleagues, noted.
The investigators measured membranous PSMA expression in 38 patients with castration-specific prostate cancer tissue biopsies and 60 patients with castration-resistant prostate cancer tissue biopsies. The association among PSMA expression, molecular aberrations (found on next-generation sequencing), and clinical outcome was explored.
For patients with castration-resistant prostate cancer, membranous PSMA expression scores were significantly higher than those for patients with castration-specific biopsies (median H-score 55.0 vs. 17.5, respectively). Patients with higher membranous PSMA expression also had higher Gleason grades (P = .04) and shorter overall survival (P = .006). In addition, the authors noted that 16 of the 38 patients with castration-specific prostate cancer (42%) tested negative for membranous PSMA expression, compared with patients with castration-resistant prostate cancer(27% tested negative).
Upon subsequent genomic analysis, patients with castration-resistant cancer who had deleterious DNA damage repair aberrations displayed higher membranous PSMA expression than those without those same aberrations. In 9 of the 11 patients who responded to PARP inhibition, membranous PSMA H-scores were above the median rate.
“The association between [membranous ] PSMA expression and [DNA damage repair] aberrations was validated in an independent cohort with known [DNA damage repair] aberrations,” the authors observed.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.
