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

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Schweizer, MT; Ha, G; Gulati, R; Brown, LC; McKay, RR; Dorff, T; Hoge, ACH; Reichel, J; Vats, P; Kilari, D; Patel, V; Oh, WK; Chinnaiyan, A ...
Published in: JCO Precis Oncol
2020

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-näıve versus chemotherapypretreated 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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Published In

JCO Precis Oncol

DOI

EISSN

2473-4284

Publication Date

2020

Volume

4

Start / End Page

382 / 392

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Schweizer, M. T., Ha, G., Gulati, R., Brown, L. C., McKay, R. R., Dorff, T., … Alva, A. (2020). CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade. In JCO Precis Oncol (Vol. 4, pp. 382–392). United States. https://doi.org/10.1200/po.19.00383
Schweizer, Michael T., Gavin Ha, Roman Gulati, Landon C. Brown, Rana R. McKay, Tanya Dorff, Anna C. H. Hoge, et al. “CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade.” In JCO Precis Oncol, 4:382–92, 2020. https://doi.org/10.1200/po.19.00383.
Schweizer MT, Ha G, Gulati R, Brown LC, McKay RR, Dorff T, et al. CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade. In: JCO Precis Oncol. 2020. p. 382–92.
Schweizer, Michael T., et al. “CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade.JCO Precis Oncol, vol. 4, 2020, pp. 382–92. Pubmed, doi:10.1200/po.19.00383.
Schweizer MT, Ha G, Gulati R, Brown LC, McKay RR, Dorff T, Hoge ACH, Reichel J, Vats P, Kilari D, Patel V, Oh WK, Chinnaiyan A, Pritchard CC, Armstrong AJ, Montgomery RB, Alva A. CDK12-Mutated Prostate Cancer: Clinical Outcomes With Standard Therapies and Immune Checkpoint Blockade. JCO Precis Oncol. 2020. p. 382–392.

Published In

JCO Precis Oncol

DOI

EISSN

2473-4284

Publication Date

2020

Volume

4

Start / End Page

382 / 392

Location

United States

Related Subject Headings

  • 3211 Oncology and carcinogenesis