Alan H. Bryce, MD, discusses potential biomarkers of response to immunotherapy in prostate cancer.
Alan H. Bryce, MD, assistant professor of medicine, Mayo Clinic, discusses potential biomarkers of response to immunotherapy in prostate cancer.
Checkpoint inhibitors have shown limited success in prostate cancer, which could be due, in part, to poor patient selection. For example, patients with high microsatellite instability (MSI-H) benefit from immunotherapy. However, only 2% to 3% of patients with prostate cancer are MSI-H.
Data presented at the 2019 ESMO Congress suggest that CDK12 could be a predictor of response to checkpoint inhibition in prostate cancer. When a somatic CDK12 mutation is present in a prostate cancer cell, it leads to genomic instability and a high rate of large tandem exon duplications as well as chromosomal rearrangements, explains Bryce. Tumor mutational burden (TMB) has been investigated as another biomarker of response to immunotherapy. However, in prostate cancer, TMB-high is 4 or 5 where generally, TMB-high is considered to be 10 mutations/megabase. Notably, TMB is considered to be a surrogate for neoantigens which could lead back to CDK12, adds Bryce.
In addition to checkpoint inhibitors, bispecific antibodies and CAR T-cell therapies are also under investigation, concludes Bryce.