In a single-center retrospective study reported as a research letter in JAMA Oncology, Zang et al found that high tumor mutational burden (TMB) was associated with better outcomes of checkpoint inhibition in patients with metastatic castration-resistant prostate cancer.
Study Details
The study involved 23 patients with metastatic castration-resistant prostate cancer treated with pembrolizumab at City of Hope National Medical Center between 2014 and 2023. Patients must have received no other prior immunotherapy. Next-generation sequencing was performed to determine TMB status, defined as low (0–5 mut/MB), medium (5–10 mut/MB), and high (≥ 10 mut/MB). Overall, 10 patients were classified as TMB-high and 13 as TMB-low/medium.
Key Findings
Objective response was observed in 50% of patients in the TMB-high group—including complete response in two patients—vs 0% of the TMB-low/medium group.
Prostate-specific antigen (PSA) responses of 50% reduction (PSA50) were observed in 50% of the TMB-high group vs 0% of the TMB-low/medium group. The two patients in the TMB-high group with complete response had PSA90 responses.
Median progression-free survival was 19.34 months in the TMB-high group vs 2.53 months in the TMB-low/medium group (hazard ratio [HR] = 0.08, 95% confidence interval [CI] = 0.02–0.40, P < .001). A trend toward improved overall survival was observed in the TMB-high group (HR = 0.37, 95% CI = 0.11–1.19, P = .08).
The investigators concluded, “In this retrospective cohort study, we sought to identify whether TMB status was associated with response to checkpoint inhibitor therapy in metastatic castration-resistant prostate cancer. Although only a small subset of metastatic castration-resistant prostate cancer is characterized by a high TMB, the findings of this study suggest that it may be associated with a longer progression-free survival with checkpoint inhibitor therapy. There were two noted patients in the TMB-high cohort who achieved PSA90 responses and complete response.”
Peter D. Zang, MD, of City of Hope Comprehensive Cancer Center, Duarte, CA, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
