No benefit to adding subablative multisite SBRT to ICI monotherapy for advanced solid tumours

Adding subablative stereotactic body radiotherapy (SBRT) concurrently to immune checkpoint inhibitor (ICI) monotherapy does little to improve survival outcomes in patients with advanced solid tumours, as shown in the phase II CHEERS trial.

CHEERS included 99 adult patients (mean age 66 years, 79 percent women) with locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, or nonsmall cell lung carcinoma. These patients were randomly assigned to receive anti–PD-1/PD-1 ligand 1 ICIs alone as per standard of care (control arm, n=52) or combined with SBRT 3 × 8 gray to a maximum of 3 lesions prior to the second or third ICI cycle, depending on the frequency of administration (experimental arm, n=47).

Of the patients, 72 (75 percent) had more than 3 tumour lesions and 65 (68 percent) had received at least 1 previous line of systemic treatment at time of inclusion. Seven patients in the experimental arm did not complete the study-prescribed radiotherapy course owing to early disease progression (n=5) or intercurrent illness (n=2). The median follow-up was 12.5 months.

The primary endpoint of progression-free survival (as per immune Response Evaluation Criteria in Solid Tumors) was not significantly different between the control arm and the experimental arm (median, 2.8 vs 4.4 months, respectively; hazard ratio [HR], 0.95, 95 percent confidence interval [CI], 0.58–1.53; p=0.82).

Likewise, the control arm did not differ much from the experimental arm in terms of overall survival (11.0 vs 14.3 months; HR, 0.82, 95 percent CI, 0.48–1.41; p=0.47) and in objective response rate (22 percent vs 27 percent; p=0.56). This was despite a local control rate of 75 percent in irradiated patients.

In terms of safety, acute treatment-related toxic effects of any grade and grade ≥3 were recorded in 79 percent and 18 percent of patients in the control arm vs 78 percent and 18 percent of those in the experimental arm, respectively. None of the patients had grade 5 adverse events.