What is the role of immunotherapy in the treatment of prostate cancer?

From the Guidelines

Immunotherapy is a viable treatment option for prostate cancer, particularly for patients with metastatic castration-resistant prostate cancer, and Sipuleucel-T is the most established immunotherapy for this indication, as evidenced by the IMPACT trial 1. The use of immunotherapy in prostate cancer has been explored in various studies, with Sipuleucel-T being the most well-established option. This treatment involves collecting a patient's immune cells, exposing them to a prostate cancer protein, and then reinfusing them to stimulate an immune response against the cancer.

• The typical regimen consists of three infusions given two weeks apart.
• Other immunotherapy approaches being investigated include immune checkpoint inhibitors like pembrolizumab and ipilimumab, though these are not yet standard treatments for prostate cancer outside of clinical trials.
• CAR T-cell therapy and therapeutic vaccines such as PROSTVAC are also under investigation. According to the NCCN Guidelines for Prostate Cancer, version 4.2023 1, immunotherapy is considered a treatment option for patients with metastatic castration-resistant prostate cancer, and the guidelines emphasize a shared decision-making approach based on patient preferences, prior treatment exposures, and potential side effects.
• The guidelines recommend the sequential addition of certain secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies in the metastatic CRPC setting.
• The NCCN Prostate Cancer Panel emphasizes the importance of patient selection and consideration of potential side effects when choosing a treatment option. In terms of efficacy, the IMPACT trial demonstrated a statistically significant 4.1-month median overall survival advantage with Sipuleucel-T versus placebo (HR, 0.78; 95% CI, 0.61 to 0.98; P .03) 1.
• The COU-302 trial also demonstrated improved overall survival with abiraterone acetate plus prednisone versus placebo plus prednisone in patients with chemotherapy-naïve, asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (HR 0.79; 95% CI 0.66–0.95) 1. Overall, immunotherapy, particularly Sipuleucel-T, is a viable treatment option for patients with metastatic castration-resistant prostate cancer, and should be considered in the context of a shared decision-making approach, taking into account patient preferences, prior treatment exposures, and potential side effects.

From the FDA Drug Label

PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. For autologous use only. For intravenous use only. Administer 3 doses at approximately 2-week intervals.

Immunotherapy for Prostate Cancer: Sipuleucel-T (PROVENGE) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. The recommended dosage is 3 doses at approximately 2-week intervals, administered intravenously over a period of approximately 60 minutes 2.

From the Research

Immunotherapy for Prostate Cancer

• Immunotherapy is a promising treatment option for prostate cancer, with some documented benefits 3.
• Prostate cancer is considered an immunologically "cold" tumor, with low tumor mutation burden and low expression of PD-L1, making it challenging to treat with immunotherapy 3.
• Sipuleucel-T (Provenge) is the first FDA-approved immunotherapeutic agent for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC), demonstrating a benefit in overall survival 3, 4, 5, 6.

Types of Immunotherapy

• Sipuleucel-T is an autologous cellular therapy that primes autologous antigen-presenting cells against the prostatic acid phosphatase (PAP) antigen 4.
• Other immunotherapies, such as vaccines (e.g., PROSTVAC-VF) and immune checkpoint inhibitors (e.g., ipilimumab), are being developed and investigated for the treatment of prostate cancer 4, 7.
• Adoptive CAR-T cell therapy is also being explored as a potential treatment option for prostate cancer 7.

Challenges and Future Directions

• The existence of a large heterogeneity in genomic alterations and a complex tumor microenvironment in prostate cancer suggests the need for identifying new immunotherapeutic targets and designing personalized immunotherapy strategies 3.
• The racial differences in immunological responses between men of diverse ethnicities merit further investigation to improve the efficacy of immunotherapy and better patient selection in prostate cancer 3.
• Combining different immunotherapy approaches and selecting them in a highly personalized way may be necessary to overcome the immunosuppressive mechanisms in the tumor microenvironment 7.