A phase II trial presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting demonstrated that adding nivolumab to standard trimodality therapy significantly improves outcomes in men with high-volume Gleason Grade Group 5 prostate cancer. The study, led by Dr. John Michael Bryant from Moffitt Cancer Center, found that the combination of nivolumab, androgen deprivation therapy (ADT), and radiation therapy led to a higher rate of freedom from biochemical recurrence compared to historical controls.
Study Design and Patient Population
The trial enrolled 34 patients with high-volume (>30% core positivity) localized or oligometastatic Grade Group 5 prostate cancer between September 2018 and April 2021. Patients received nivolumab every two weeks for four doses, along with standard-of-care trimodality therapy consisting of ADT, external beam radiation therapy (EBRT), and brachytherapy. The primary endpoint was 2-year freedom from biochemical recurrence, with a target rate of ≥90%.
The study also included an external contemporary control cohort of 45 patients treated with standard-of-care trimodality therapy at the same institution between January 2013 and November 2021. These patients were retrospectively identified to meet all enrollment criteria and had at least two years of active follow-up.
Key Findings
The 2-year freedom from biochemical recurrence in the nivolumab cohort was 90.3%, significantly exceeding the historical control rate of 75% (p=0.025). The median freedom from biochemical recurrence survival was 58.6 months. Importantly, no grade ≥4 toxicities were observed.
Further analysis revealed that the nivolumab cohort demonstrated a significant improvement in 3-year freedom from biochemical recurrence compared to controls (90.4% versus 68.8%, p=0.027).
Multivariable analysis confirmed that the addition of nivolumab was significantly associated with improved biochemical recurrence rates (HR: 0.13, p=0.008).
Baseline Characteristics
Baseline characteristics showed that trial patients were younger (65.5 versus 69 years, p=0.018) and had more advanced disease, including higher rates of lymph node involvement (16% versus 7%) and distant metastases (9.4% versus 0%). They were also less likely to have had nodal irradiation (16% versus 44%, p=0.008).
Clinical Implications
Dr. Bryant concluded that the addition of nivolumab to trimodality therapy was associated with improved freedom from biochemical recurrence in men with high-volume Gleason Grade Group 5 disease, compared to both pre-defined historic control rates and contemporary controls, despite the nivolumab group having higher baseline rates of metastatic disease and less elective nodal irradiation. These findings suggest that nivolumab may help overcome the innate immune resistance of aggressive prostate cancer, potentially improving disease control and long-term outcomes.
