Assessment of PSA responses and changes in the rate of tumor growth (g-rate) with immune checkpoint inhibitors in US Veterans with prostate cancer

• Published in: Seminars in oncology Vol. 51; no. 3-4; pp. 59 - 68
• Main Authors: Leuva, Harshraj, Moran, George, Jamaleddine, Nader, Meseha, Mina, Zhou, Mengxi, Im, Yunju, Rosenberg, Ta-Chueh Melody, Park, Yeun-Hee Anna, Luhrs, Carol, Bates, Susan E., Faiena, Izak
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Aged; Androstenes; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides - therapeutic use; g-rate; Growth rate; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Male; Metastatic prostate cancer; Middle Aged; Nitriles - therapeutic use; Phenylthiohydantoin - administration & dosage; Phenylthiohydantoin - therapeutic use; Prostate-Specific Antigen - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Retrospective Studies; Tumor response; United States - epidemiology; Veterans - statistics & numerical data; United States; Metastatic prostate cancer; Immune checkpoint inhibitors; g-rate; Growth rate; Tumor response
• ISSN: 0093-7754; 1532-8708; 1532-8708
• DOI: 10.1053/j.seminoncol.2024.04.002

We examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone or enzalutamide to assess ICI efficacy in the real-world. We queried the VA corporate data warehouse (CDW) to identify Veterans with a diagnosis of PC who received ICI for any malignancy and had ≥1 PSA measurement while receiving ICI. To evaluate ICI monotherapy, we restricted analysis to Veterans who had not received LHRH agonists/antagonists, PC-directed medical therapy, or radiation/extirpative surgery of the bladder/prostate within and preceding the duration of ICI administration. For ICI combination analysis, we identified Veterans who received abiraterone or enzalutamide for PC while on ICI. We calculated rates of tumor (PSA) growth (g-rates), comparing them to a 1:2 matched reference cohort. We identified 787 Veterans with PC and ≥1 PSA measurement while receiving an ICI. Median duration of ICI therapy was 155 days. 223 Veterans received ICI monotherapy, with only 17(8%) having a reduction in PSA (median decline = 43%). 12 (5%) had PSA declines >30% (PSA30) which included 6 (3%) who had PSA reductions greater than 50% (PSA50). Median g-rates for ICI plus abiraterone (n = 20) or enzalutamide (n = 31) were 0.000689/d−1 and 0.002819/d−1, respectively, and were statistically insignificant compared to g-rates of matched cohorts receiving abiraterone (g = 0.000925/d−1, P = 0.73) or enzalutamide (g = 0.001929/d−1, P = 0.58) alone. Our data align with clinical trial data in PC, demonstrating limited benefit from ICI monotherapy and predicting no survival benefit from simultaneous abiraterone or enzalutamide with an ICI using g-rate.