CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade

医学 恩扎鲁胺 前列腺癌 内科学 肿瘤科 前列腺特异性抗原 癌症 雄激素受体
作者
Michael T. Schweizer,Gavin Ha,Roman Gulati,Landon C. Brown,Rana R. McKay,Tanya B. Dorff,Anna C. H. Hoge,Jonathan Reichel,Pankaj Vats,Deepak Kilari,Vaibhav G. Patel,William Oh,Arul M. Chinnaiyan,Colin C. Pritchard,Andrew J. Armstrong,Bruce Montgomery,Ajjai Alva
出处
期刊:JCO precision oncology [American Society of Clinical Oncology]
卷期号: (4): 382-392 被引量:65
标识
DOI:10.1200/po.19.00383
摘要

PURPOSE Translational studies have shown that CDK12 mutations may delineate an immunoresponsive subgroup of prostate cancer, characterized by high neo-antigen burden. Given that these mutations may define a clinically distinct subgroup, we sought to describe outcomes to standard drugs and checkpoint inhibitors (CPI). PATIENTS AND METHODS Clinical data from consecutive patients with CDK12 mutations were retrospectively collected from 7 centers. Several clinical-grade sequencing assays were used to assess CDK12 status. Descriptive statistics included PSA50 response rate (≥ 50% decline in prostate-specific antigen from baseline) and clinical/radiographic progression-free survival (PFS). RESULTS Of 52 patients with CDK12-mutated prostate cancer, 27 (52%) had detected biallelic CDK12 alterations. At diagnosis, 44 (88%) had Gleason grade group 4-5, 52% had T3-T4, and 14 (27%) had M1 disease. Median follow-up was 8.2 years (95% CI, 5.6 to 11.1 years), and 49 (94%) developed metastatic disease. Median overall survival from metastasis was 3.9 years (95% CI, 3.2 to 8.1 years). Unconfirmed PSA50 response rates to abiraterone and enzalutamide in the first-line castration-resistant prostate cancer setting were 11 of 17 (65%) and 9 of 12 (75%), respectively. Median PFS on first-line abiraterone and enzalutamide was short, at 8.2 months (95% CI, 6.6 to 12.6 months) and 10.6 months (95% CI, 10.2 months to not reached), respectively. Nineteen patients received CPI therapy. PSA50 responses to CPI were noted in 11%, and PFS was short; however, the estimated 9-month PFS was 23%. PFS was higher in chemotherapy-naïve versus chemotherapy-pretreated patients (median PFS: not reached v 2.1 months, P = .004). CONCLUSION CDK12 mutations define an aggressive prostate cancer subgroup, with a high rate of metastases and short overall survival. CPI may be effective in a minority of these patients, and exploratory analysis supports using anti–programmed cell death protein 1 drugs early. Prospective studies testing CPI in this subset of patients with prostate cancer are warranted.
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