Abstract
In patients with metastatic castration-resistant prostate cancer, pembrolizumab showed efficacy.
Major Finding: In patients with metastatic castration-resistant prostate cancer, pembrolizumab showed efficacy.
Concept: The phase II trial showed modest objective response rates, but responses attained were durable.
Impact: Some immunotherapies may be effective in this disease; biomarkers for response must be identified.
Metastatic castration-resistant prostate cancer (mCRPC) is characterized by an immunosuppressive tumor microenvironment, implying that immunotherapies may have limited efficacy. However, there is some evidence of antitumor activity for the anti–PD-1 therapy pembrolizumab in patients with mCRPC. Antonarakis and colleagues have reported results from the first three of five cohorts of patients with metastatic or locally confined but inoperable CRPC recruited into an open-label, phase II clinical trial of pembrolizumab monotherapy. All patients had previously received treatment with one or more targeted endocrine therapies and one to two regimens of chemotherapy, one of which was required to have included docetaxel. Across all three cohorts, 258 patients were enrolled, with 133 in cohort 1 (patients with PD-L1–positive disease), 66 in cohort 2 (patients with PD-L1–negative disease), and 59 in cohort 3 (patients with bone-predominant disease, regardless of PD-L1 status). Median overall survival was 9.5 months in cohort 1, 7.9 months in cohort 2, and 14.1 months in cohort 3. The objective response rate (ORR) was 5% (seven of 133 patients) in cohort 1, with two patients experiencing complete radiographic responses, whereas the ORR was 3% (two of 66 patients) in cohort 2. Although the ORR in these cohorts was low, the responses were long lasting, with the median duration of response being 16.8 months. Treatment-related adverse events, the most common of which were fatigue, diarrhea, and decreased appetite, were observed in 60% (155 of 258) of patients, and two deaths were determined to have been treatment related. Exploratory next-generation sequencing studies for predictive biomarkers were not conclusive. Limitations of the study include lack of randomization, lack of a control group, and short follow-up period. Overall, the results of this trial indicate that despite the immunosuppressive tumor microenvironment observed in mCRPC, anti–PD-1 therapy is effective in some patients, and further research should focus on identifying which patients are most likely to respond.
Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.
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