The addition of stereotactic body radiation therapy (SBRT) to nivolumab (Opdivo) plus ipilimumab (Yervoy) did not improve response rates or survival compared with the immunotherapy doublet alone in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), according to findings from the randomized phase 2 CheckPRO trial (CA209-8TY; NCT05655715) published in Journal for ImmunoTherapy of Cancer.¹
Among evaluable patients, the confirmed prostate-specific antigen (PSA) response rate was 21.6% (95% CI, 9.8%-38.2%; n = 8 of 37) with SBRT plus nivolumab/ipilimumab (arm A) vs 20.5% (95% CI, 9.8%-35.3%; n = 9 of 44) with nivolumab/ipilimumab alone (arm B). The objective response rate (ORR) among patients with measurable disease was 16.7% (95% CI, 4.7%-37.4%; n = 4 of 24) in arm A and 22.2% (95% CI, 10.1%-39.2%; n = 8 of 36) in arm B, for an overall cohort ORR of 20%. Median overall survival (OS) was 10.2 months (95% CI, 7.1-15.2) in arm A and 9.2 months (95% CI, 7.1-14.4) in arm B.
"This single-center, investigator-initiated, randomized phase II trial successfully met the primary endpoint of PSA response for ≥8 patients in arms A and B, suggesting that the combination treatment with nivolumab and ipilimumab is beneficial for a subgroup of patients with mCRPC," the study authors wrote. "However, the addition of SBRT did not increase the response rates or survival outcomes in the evaluable nor the ITT patient population, indicating that our primary hypothesis was not supported."
CheckPRO Trial of Nivolumab/Ipilimumab ± SBRT in mCRPC: Key Findings
- Adding SBRT did not improve PSA response, ORR, PFS, or OS compared with nivolumab/ipilimumab alone; the trial's primary hypothesis of an SBRT-induced abscopal effect was not supported.
- The confirmed PSA response rate and ORR met the prespecified bar for the nivolumab/ipilimumab combination to be considered "promising" in both arms.
- Median OS was similar between arms A and B (10.2 vs 9.2 months), and patients without a PFS event within 6 months had substantially longer OS (27.6 vs 5.3 months).
How was CheckPRO designed?
CheckPRO was a single-center, investigator-initiated trial conducted at Herlev and Gentofte Hospital in Copenhagen, Denmark, that enrolled patients with histologically confirmed mCRPC who had received at least 2 prior lines of therapy in the metastatic setting, including at least 1 androgen receptor pathway inhibitor and 1 taxane-based chemotherapy regimen, a performance status of 0 or 1, no prior immunotherapy, and a metastatic lesion eligible for SBRT.1,2
Between November 2019 and January 2024, 91 patients were randomly assigned 1:1 to SBRT at 24 Gy in 3 fractions over 1 week plus nivolumab at 3 mg/kg, and ipilimumab at 1 mg/kg every 3 weeks for 4 cycles (arm A), or the same systemic regimen without SBRT (arm B); both arms continued nivolumab monotherapy at 480 mg every 4 weeks for up to 52 weeks.1
The co-primary end points were confirmed PSA response rate (PSA50) and ORR per Prostate Cancer Working Group 3 RECIST 1.1 criteria.
Eight patients in arm A and 2 in arm B did not receive the intended therapy because of clinical deterioration before treatment initiation, which was driven largely by the SBRT planning period in arm A, leaving 37 and 44 patients, respectively, evaluable for response, survival, and safety. Nearly all patients (97%) had received 3 or more prior lines of therapy, and more than 80% had bone metastases at baseline.
