The immune system has the remarkable ability to kills cells that can cause harm, such as infected cells or cancer cells. However, in most patients with progressing cancer, anti-cancer immune responses either never developed or have been turned off by the cancer. One way to fight cancer is to hack the immune system, retraining immune cells to respond to the malfunctioning cancer cells.
Sipuleucel-T Immunotherapy
Sipuleucel-T (Provenge®) is a cell-based prostate cancer vaccine that has been approved by the FDA for men with metastatic prostate cancer that is resistant to hormone therapy. This treatment is meant for men with minimal or no pain, and is most commonly given before chemotherapy, although it appears to be effective in some men even after chemotherapy.
The treatment process involves filtering out your immune cells, stimulating them in a lab to fight prostate cancer, and then reinfusing those cells back into you intravenously (IV). This process is repeated every 2 weeks for a total of 3 treatments. The goal is to stimulate your own immune system to fight the cancer cells. This immunotherapy does not lower PSA, treat symptoms, or delay disease progression—however, it has been shown to prolong life. There are ongoing studies attempting to clarify exactly how this treatment works. Sipuleucel-T should only be considered in cases where the patient has a slow-growing tumor and does not need urgent cancer shrinkage (which can be achieved effectively with other agents).
This treatment can only be given in certain centers, and you should discuss with your doctor whether this treatment is appropriate for you.
The side effects of Sipuleucel-T are usually limited to the few days after infusion of the stimulated cells. You can sometimes experience a flu-like illness with fever, chills, nausea, and bone/muscle aches. This generally resolves within 3 days and can be treated with acetaminophen.
Pembrolizumab
Pembrolizumab (Keytruda®) is a type of “immune checkpoint inhibitor,” which are a class of immunotherapies that block chemical signals that mask cancer cells and activate tumor-killing immune cells. Pembrolizumab was approved by the FDA in 2017 for the treatment of all solid tumors, including prostate cancer, that have certain characteristic mutation patterns in their genes. Today, this means that the prostate cancer has mutations in mismatch repair genes (called dMMR), exhibits high microsatellite instability (MSI-H), or has a high tumor mutational burden (TMB-H). Patients who qualify for this therapy must have progressed on prior treatment and have no satisfactory alternative treatment options. Hence, pembrolizumab would typically be considered after other available effective treatments (such as sipuleucel-T, abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223, etc.) have been used or ruled out.
Studies suggest that approximately 5%, and perhaps up to 10% of patients with metastatic prostate cancer have evidence of MMR mutations and/or MSI in their tumors. Some of these mutations may be inherited, and may be associated with Lynch syndrome, a condition which predisposes individuals to higher risks of developing certain cancers such as colorectal cancer. At present, regardless of family history, MMR deficiency, MSI, and TMB are determined by biomarker tests performed on biopsies or tumor material from prostate surgery.
Pembrolizumab is delivered intravenously once every 3 weeks. The most common side effects are fatigue, cough, shortness of breath, nausea, constipation, itching, rash, and decreased appetite. Because it works by modifying the immune system, there are rare but serious side effects related to overactive immune responses which are typically treated by stopping the drug and, in some cases, starting steroid medications to suppress the immune reactions.
Want more information about a prostate cancer diagnosis and treatment options? Download or order a print copy of the Prostate Cancer Patient Guide.