Combining nivolumab with standard-of-care radiotherapy significantly improved freedom from biochemical recurrence (FFBR) in patients with Gleason grade group 5 (GG5) prostate cancer, according to a phase 2 trial presented at the 2024 American Society for Radiation Oncology Annual Meeting (ASTRO). The study suggests a promising approach for managing high-risk prostate cancer.
Improved Biochemical Recurrence Outcomes
At 2 years, the FFBR rate was 90.3% among patients who received nivolumab plus radiotherapy, compared with a historical control rate of 75% (P = .025). The median FFBR was 58.6 months with nivolumab-based treatment, and no grade 4 or higher toxicities were observed. At 3 years, the FFBR rate was 90.4% in the nivolumab arm versus 68.8% in a contemporary control cohort who received standard-of-care radiotherapy (P = .027).
"The addition of [nivolumab] to trimodality therapy was associated with improvements in [FFBR] in [patients] with high volume GG5 prostate cancer as compared with the predefined historic control rate and also the contemporary controls despite having higher baseline rate of metastatic disease and no elective nodal irradiation," said John Michael Bryant, MD, chief radiation oncology resident at the H. Lee Moffitt Cancer Center and Research Institute.
Multivariate Analysis
Adjusted multivariate analysis showed that adding nivolumab significantly correlated with improved biochemical recurrence outcomes compared with standard of care alone (P = .008). Stage IVA (P = .022) and stage IVB disease (P = .031) were significantly associated with biochemical recurrence outcomes when compared to the contemporary control cohort.
Pathological Response and Biomarkers
Patients with a late pathological response and eventual disease progression generally had multiple metastatic sites, compared with early responders who tended to have a single metastatic site at the time of progression. Biomarker analysis showed that the Ricketts Gene Signature significantly correlated with both early pathological and radiographic responses. This signature comprised 13 genes associated with immunosuppression, including CD274, IDO1, FASLG, CTLA4, PDCD1, and LAG3. A low risk for having the Ricketts signature was the only factor significantly associated with response outcomes based on adjusted multivariate analysis (P = .04).
"Early pathologic response, characterized by a lower residual tumor burden and higher immune marker expression, was associated with better clinical outcomes," Bryant noted. "The Decipher Ricketts Immunosuppression score is a potential biomarker that may help with patient selection in the future for this type of therapy."
Trial Design and Patient Population
The phase 2 trial was conducted at the H. Lee Moffitt Cancer Center & Research Institute. Eligible patients had high volume localized or oligometastatic GG5 prostate cancer. The trial initially included 34 patients, with 2 ultimately being withdrawn from the analysis. Patients received 240 mg of nivolumab every 2 weeks for 4 doses, combined with standard trimodality therapy consisting of androgen deprivation therapy, external beam radiotherapy, and brachytherapy. The primary endpoint was a 2-year FFBR of 90% or greater.
Outcomes among patients who received nivolumab-based therapy were compared with those of an external contemporary control cohort including 45 patients who received standard-of-care radiotherapy at the same institution from January 2013 to November 2021. Patients in the nivolumab cohort tended to be younger than those in the contemporary control cohort (P = .018). A higher proportion of patients in the control group had stage IIIC disease (93.3%) compared with those in the nivolumab cohort (75.0%; P = .041). Also, 84.4% of patients who received nivolumab had no nodal irradiation field compared with 55.6% in the control group (P = .008).
Conclusion
"These data from the study ultimately support larger randomized controlled trials in order to confirm the findings [from] this early phase 2 [study]," Bryant concluded.
