Moffitt Study Shows Promising Results for Treating Aggressive Prostate Cancer with Immunotherapy
Prostate cancer is one of the most common types of cancer in men, but when it reaches Gleason Group 5, prostate cancer represents the most advanced and high-risk cases of the disease, often with a high likelihood of recurrence or progression despite standard treatments. Moffitt Cancer Center researchers recently investigated whether combining immunotherapy drug nivolumab with the existing standard of care could offer better outcomes for these high-risk patients in a phase 2 clinical trial. The results were promising, suggesting a potential new avenue for treatment.
Traditionally, one of the standards of care for advanced prostate cancer involves a combination of three primary treatments.
- Androgen Deprivation Therapy: This treatment reduces the levels of hormones (androgens), such as testosterone, which are known to fuel the growth of prostate cancer cells.
- External Beam Radiation Therapy: This approach delivers radiation from outside the body to kill cancer cells in the prostate.
- High-Dose Rate Brachytherapy: A form of internal radiation where radioactive material is placed directly inside or near the tumor to deliver high doses of radiation to the cancerous cells with precision.
Despite these efforts, many men with Gleason Group 5 prostate cancer still experience a recurrence of the disease or progression to metastatic cancer. This unmet medical need led Moffitt researchers to explore whether adding immunotherapy could enhance treatment outcomes. The results of the phase 2 trial analysis were presented at the 2024 American Society for Radiation Oncology annual meeting.
The study involved 34 men diagnosed with localized Gleason Group 5 prostate cancer. These men were treated with nivolumab alongside androgen deprivation therapy, radiation and brachytherapy. Nivolumab is part of a class of drugs called immune checkpoint inhibitors, which work by unmasking cancer cells, allowing the immune system to better recognize and attack them.
Previous attempts to treat prostate cancer with immunotherapy alone were largely ineffective because the disease has the ability hide from the immune system. Recent evidence, however, suggests that hormone therapy and radiation could stimulate the immune system, making it more effective in recognizing the tumor. This study provided the first real evidence of the efficacy of this combination.
John Michael Bryant, MD
“By giving high doses of radiation (known as ablative doses), along with hormone therapy, the tumor environment can be altered to allow the immune system to better recognize the cancer and target it more effectively,” said John Michael Bryant, MD, a radiation oncology resident at Moffitt who worked as part of the study team.
Patients in the study received two cycles of nivolumab before the first fraction of brachytherapy to “prime” the immune system. The immunotherapy was continued after the initial brachytherapy session to ensure the immune system remained active during subsequent treatment cycles.
The key outcome of the study was the improvement in biochemical recurrence-free survival. Biochemical recurrence refers to an increase in prostate-specific antigen (PSA) levels in the blood, which can be a sign that prostate cancer has returned. In this study, the researchers compared the rate of biochemical recurrence between the patients who received the combined treatment with nivolumab and those who only received standard of care.
“Historically, patients with Gleason Group 5 prostate cancer treated with the standard therapies at Moffitt had a biochemical failure rate of approximately 25% after two years. However, the addition of nivolumab in this trial reduced the rate of biochemical failure to just 10%, meaning 90% of patients in the nivolumab group remained free from cancer recurrence over the two-year period,” Bryant said.
Another exciting finding from the study was the identification of a potential biomarker that could help predict which patients would respond best to the combination therapy. The biomarker, referred to as Ricketts immunosuppression, is composed of about 13 genes that were found to correlate with a patient’s response to the treatment. Patients who had an early pathological response were more likely to have this biomarker.
This biomarker could have significant implications for future prostate cancer treatment. By testing patients for the presence of this biomarker at the time of diagnosis, clinicians could potentially identify which individuals are most likely to benefit from the addition of immune checkpoint inhibitor therapy to radiation-based standard of care therapy, allowing for more personalized and effective treatment plans.
Although the study results are promising, Bryant emphasizes that further work is required before this combination treatment can be integrated into the standard of care. The next step is to conduct randomized trials to confirm the findings and validate the safety and efficacy of adding nivolumab to the treatment regimen for Gleason Group 5 prostate cancer. These trials will also focus on prospectively validating the Ricketts immunosuppression biomarker as a tool for selecting patients best suited for this approach.
