Clinical efficacy of hypofractionated radiotherapy combined with immune checkpoint inhibitors in treating advanced metastatic solid tumors

Objective To investigate the efficacy of hypofractionated radiotherapy (HFRT) combined with programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors in sequential with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) for the treatment of advanced metastatic solid tumors.

Methods A prospective single-center single-arm study was designed for patients failed standard treatments for advanced refractory solid tumors in the Department of Radiotherapy of Jiangyin Hospital affiliated to Nantong University, and eligible patients were given quadruple therapy: HFRT (5 to 8 Gy × 2 to 3 f) once every 21 days for at least 2 cycles; 200 μg GM-CSF from the 1st to 7th day of radiotherapy, and 2 million IU IL-2 from the 8thto 14th day. Within 1 week after the completion of HFRT, PD-1/PD-L1 inhibitors were used for treatment. The above treatment strategy was repeated. GM-CSF and IL-2 were treated for 6 cycles, followed by maintenance with PD-1/PD-L1 inhibitors until disease progression (PD) or intolerable toxicity occurred. Objective response rate (ORR) and treatment-related adverse events were analyzed.

Results From January 9, 2021 to June 15, 2023, totally 40 patients were enrolled, with follow-up of 2.8 to 31.0 months and a median follow-up of 9.9 months, and 39 patients (97.5%) completed at least one time tumorsite evaluation within the non-radiotherapy target area. 97.5% of patients had cancers, 2.5% had soft tissue sarcomas, and 20.0% had received immune checkpoint inhibitors (ICIs) at baseline check. The ORR was 30.8%, and the disease control rate (DCR) was 71.8%; the ORR for non-small cell lung cancer (NSCLC) was 28.6%, and the DCR was 57.1%; the ORR for colorectal cancer was 14.3%, and the DCR was 71.4%; the ORR for gastric cancer was 16.7%, and the DCR was 66.7%; 28 patients (70.0%) had treatment-related adverse events (TRAE), 4 patients (10%) had TRAE≥level 3, and the most common types of TRAE were fatigue, fever and hypothyroidism.

Conclusion The treatment of HFRT combined with immune checkpoint inhibitors in sequential with GM-CSF and IL-2 is well tolerated and toxicity accepted in patients with advanced metastatic solid tumors, which may provide a new method for salvage treatment of patients with advanced metastatic solid tumors.