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Immune Checkpoint Therapies in Prostate Cancer.

ABSTRACT: Advanced prostate cancer is the second leading cause of death from cancer in the United States. In the era of cancer immunotherapy, it was the first malignancy to demonstrate improved survival with a cancer-specific vaccine, thus proving that prostate cancer is an immune-responsive disease. However, the success with immune checkpoint therapies in metastatic prostate cancer has been limited to date with only a subset of patients experiencing clinical benefit. The relative lack of response could be attributed to patient selection based on clinical attributes and the tumor microenvironment. Here, we review the current data on immune checkpoint therapies in prostate cancer and propose future directions.

SUBMITTER: Goswami S

PROVIDER: S-EPMC4847149 | biostudies-literature | 2016 Mar-Apr

REPOSITORIES: biostudies-literature

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Immune Checkpoint Therapies in Prostate Cancer.

Goswami Sangeeta S Aparicio Ana A Subudhi Sumit K SK

Cancer journal (Sudbury, Mass.) 20160301 2

Advanced prostate cancer is the second leading cause of death from cancer in the United States. In the era of cancer immunotherapy, it was the first malignancy to demonstrate improved survival with a cancer-specific vaccine, thus proving that prostate cancer is an immune-responsive disease. However, the success with immune checkpoint therapies in metastatic prostate cancer has been limited to date with only a subset of patients experiencing clinical benefit. The relative lack of response could b ...[more]

PMID: 27111907

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Project description:PurposeTranslational 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 methodsClinical 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).ResultsOf 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).ConclusionCDK12 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.

Dataset Information

Immune Checkpoint Therapies in Prostate Cancer.

Publications

Immune Checkpoint Therapies in Prostate Cancer.

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