(UroToday.com) The 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting held in Washington, DC between September 29th and October 2nd, 2024, was host to a prostate cancer treatment intensification session. Dr. John Michael Bryant presented the final results of a randomized phase II trial evaluating the combination of nivolumab, androgen deprivation therapy (ADT), plus radiation therapy in patients with Gleason Grade Group 5 prostate cancer.
High- and very high-risk prostate cancer account for approximately two-thirds of prostate cancer deaths, despite accounting for only one-sixth of new diagnoses. The presence of Gleason Grade Group 5 disease is independently associated with an increased risk of disease recurrence and mortality. Both radiotherapy and ADT have demonstrated the potential to improve immune responses in prostate cancer. The study investigators hypothesized that a treatment approach that adds an immune checkpoint inhibitor would be able to leverage the immunomodulating effects of radiotherapy and ADT to overcome the innate immune resistance of prostate cancer, in order to improve disease control.
This was a phase II trial conducted at the H. Lee Moffitt Cancer Center and Research Institute. This trial included men with high volume (>30% core positivity) either localized or oligometastatic Grade Group 5 prostate cancer. Overall, 34 patients were enrolled between September 2018 and April 2021. The study intervention entailed nivolumab every 2 weeks for 4 doses + standard-of-care trimodality therapy (i.e., ADT + External beam radiation therapy (EBRT)+ brachytherapy). The primary endpoint was 2-year freedom from biochemical recurrence, with a target rate of ≥90%.
The study flowchart is summarized below. This final cohort for analysis included 32 patients who completed treatment.
This study included an external contemporary control cohort, which consisted of 45 patients treated with standard-of-care trimodality therapy (ADT + EBRT + brachytherapy) at the same institution between January 2013 and November 2021, who were retrospectively identified to meet all enrollment criteria and had ≥2 years of active follow-up.
The baseline patient characteristics for the trial and contemporary control groups are summarized below. Trial patients were:
- Younger: 65.5 versus 69 years (p=0.018)
- Had more advanced disease (p=0.041)
- Lymph node involvement: 16% versus 7%
- Distant metastases: 9.4% versus 0%
- Less likely to have had nodal irradiation: 16% versus 44% (p=0.008)
The 2-year freedom from biochemical recurrence was 90.3%, exceeding this historical control rate of 75% (p=0.025). The median freedom from biochemical recurrence survival was 58.6 months. No grade ≥4 toxicities were encountered.
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).
On multivariable analysis, the addition of nivolumab was found to be significantly associated with improved biochemical recurrence rates (HR: 0.13, p=0.008).
Dr. Bryant concluded as follows:
- 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, as compared to pre-defined historic control rates and contemporary controls, despite having higher baseline rates of metastatic disease and no elective nodal irradiation.
Presented by: John Michael Bryant, MD, Radiation Oncology Resident Physician, Moffitt Cancer Center, Tampa, Fl
Written by: Rashid Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2024 ASTRO Annual Congress held in Washington, DC between September 29th and October 2nd, 2024