Adding subablative stereotactic body radiotherapy (SBRT) of a limited number of metastatic lesions to immune checkpoint inhibitor (ICI) monotherapy is safe, but did not improve overall survival (OS) or progression-free survival (PFS) in patients with advanced solid tumors, according to the results of a study published in JAMA Oncology.
Researchers conducted an open-label, multicenter, randomized phase 2 trial in 5 Belgian hospitals, enrolling patients with cancer between March 2018 and October 2020, to assess the effectiveness of adding radiotherapy to ICI compared with ICI monotherapy in patients with advanced solid tumors (CHEERS phase 2 clinical trial; ClinicalTrials.gov Identifier: NCT03511391).
The primary endpoint was PFS; secondary endpoints included OS, objective response rate, local control rate, and toxic effects.
The cancer types represented in this study included locally advanced or metastatic melanoma, renal cell carcinoma (RCC), urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC), and non-small cell lung cancer (NSCLC).
A total of 99 patients were randomly assigned 1:1 to receive anti-PD-1/PD-1 ligand 1 ICIs alone (control arm; 52 patients) or ICIs with SBRT 3×8 Gy to a maximum of 3 lesions before the second or third ICI cycle (experimental arm; 47 patients). Three patients (1 in control arm, 2 in experimental arm) eventually withdrew consent, so their results were not included in the analysis.
Of the 96 patients in the analysis, 72 had more than 3 tumor lesions and 65 had received at least 1 previous line of systemic treatment at the time of inclusion. Seven patients in the experimental arm did not complete the prescribed SBRT course due to disease progression (5 patients) or intercurrent illness (2 patients)
Median PFS was 2.8 months in the control arm and 4.4 months in the experimental arm, with a median follow-up of 12.5 months (range, 0.7-46.2; hazard ratio [HR], 0.95; 95% CI, 0.58-1.53; P =.82).
No improvement was observed in median OS between the control and experimental arms (11.0 vs 14.3 months; HR, 0.82; 95% CI, 0.48-1.41; P =.47). Local control rate was 75% in irradiated patients; however, no statistically significant difference was observed in objective response rate between the control and experimental arms (22% vs 27%; P =.56).
While no grade 5 adverse events (AEs) were reported, some patients experienced acute treatment-related toxic effects at lower grades. Any grade AEs occurred in 79% and 78% of patients in the control and experimental arms, respectively. Grade 3 or 4 adverse events occurred in 18% in the control arm and 18% in the experimental arm. Fatigue and pruritus were among the most common adverse events reported.
“In this phase 2 randomized clinical trial, while the addition of subablative multisite stereotactic radiotherapy to ICI monotherapy failed to result in any clinically meaningful abscopal effect in a diverse and largely polymetastatic patient population, the findings suggest it is safe to combine both treatment modalities in this context and offer important insights for future trial design,” the research team concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Spaas M, Sundahl N, Kruse V, et al. Checkpoint inhibitors in combination with stereotactic body radiotherapy in patients with advanced solid tumors: The CHEERS phase 2 randomized clinical trial. JAMA Oncol. Published online July 06, 2023. doi:10.1001/jamaoncol.2023.2132