No Added Benefit From SBRT in mCRPC Treated With Immunotherapy
Nivolumab plus ipilimumab showed activity in mCRPC, and while adding SBRT was safe, it did not boost efficacy in the CheckPRO trial.
3D rendered medically accurate illustration of prostate cancer: © SciePro - stock.adobe.com
In patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) demonstrated clinical activity, while the addition of stereotactic body radiation therapy (SBRT) was well tolerated but did not enhance efficacy. These findings come from the phase 2 CheckPRO trial (NCT05655715) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
The prostate-specific antigen (PSA) response rate for nivolumab plus ipilimumab and SBRT (arm A) was 21.6% (95% CI, 9.8%-38.2%) vs 20.5% (95% CI, 9.8%-35.3%) for nivolumab/ipilimumab alone (arm B). The objective response rate (ORR) was 16.7% (95% CI, 4.7%-37.4%) for arm A vs 22.2% (95 CI, 10.1%-39.2%) for arm B.
The median PSA progression-free survival (PFS) for arm A was 2.6 months (95% CI, 1.9-3.8), and for arm B it was 2.5 months (95% CI, 1.9-3.0). The radiographic PFS was 2.1 months (95% CI, 1.9-3.8) for arm A and 1.9 months (95% CI, 1.8-2.5) for arm B. Additionally, the overall survival (OS) was 10.2 months (95% CI, 7.1-14.1) for arm A and 9.2 months (95% CI, 7.1-14.1) for arm B.
“Responses were demonstrated in a subgroup of patients with mCRPC treated with [immune checkpoint inhibitors (ICI)],” Rikke Eefsen, MD, PhD, a medical oncologist from Herlev Gentofte Hospital in Copenhagen, Denmark, said during the presentation. “The addition of SBRT was safe, but it did not improve treatment outcomes.”
A total of 90 patients were enrolled and randomly assigned 1:1 to either arm A where they received SBRT at 8 Gy 3 times on a metastasis, nivolumab at 3 mg/kg intravenously every 3 weeks, and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 cycles; or arm B where they received matched nivolumab/ipilimumab.
From there, patients then went on to receive 480 mg of intravenous nivolumab every 4 weeks for up to 52 weeks. If patients had progressive disease within the 52 weeks, they had re-induction therapy.
The co-primary end point were PSA response rate, which was the benefit of more than 50% PSA decline at any time or at 12 weeks, which was confirmed 4 weeks later or progression of more than 25% PSA increase confirmed 3 weeks later; and ORR per Prostate Cancer Working Group RECIST 1.1. Secondary end points included PSA, PFS, radiographic PFS, OS, and toxicities.
Overall, 130 patients were assessed for eligibility, with 39 excluded, and 91 were randomly assigned, with 45 patients in arm A and 46 patients in arm B. During follow-up, 37 patients in arm A discontinued intervention compared with 44 in arm B. For arm A, 37 patients were analyzed, and in arm B, there were 44.
The median patient age in arm A was 72 and in arm B it was 73, an ECOG performance score of 0 was observed in 48.6% vs 47.7%, 45.9% vs 75.0% of patients had a Gleason score of 7 or more at diagnosis, and 73.0% vs 54.4% had M1 metastases at diagnosis. Additionally, 64.9% vs 81.8% had measurable disease at baseline, and 100% vs 93.2% had 3 or more prior lines of therapy.
Regarding safety, 81 patients were evaluable. Any grade adverse effect (AE) was observed in 100% of patients, and 70.4% had grade 3/4. Treatment-related AEs (TRAEs) of any grade were observed in 92.6% vs 33.3% for grade 3/4, and treatment-related serious AEs in 34.6% vs 30.9%.
Notably, any grade TRAEs included pruritus (39.5%), rash (35.8%), liver transaminase increase (22.2%), hypothyroidism (19.8%), and diarrhea (19.8%). Grade 3/4 AEs included colitis (9.9%), diarrhea (6.2%), hepatitis (4.9%), pneumonitis (3.7%), and hyperglycemia (2.5%).
“Further analyses are ongoing to identify patients with mCRPC, who most likely respond to ICI,” Eefsen concluded.
