Efficacy of PRaG therapy in microsatellite-stable metastatic colorectal cancer: a comparative analysis of PD-1/PD-L1 inhibitor-based combination therapies.

BACKGROUND: Most (95%) metastatic colorectal cancers (mCRCs) exhibit microsatellite stability (MSS) and proficiency in DNA mismatch repair (pMMR), leading to resistance to immunotherapy. To overcome this, the combination of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors with other therapeutic strategies has been explored. This study evaluated the efficacy of PRaG therapy-a combination of PD-1 inhibitors, radiotherapy, and granulocyte‒macrophage colony-stimulating factor-in comparison with other combination therapies. METHODS: MSS/pMMR mCRC patients receiving PD-1/PD-L1 inhibitor combination therapy at the Second Affiliated Hospital of Soochow University were analyzed. Patients were grouped by therapy type, and SPSS 26.0 was used to assess clinical features, survival outcomes, tumor response, and adverse reactions. RESULTS: A total of 101 patients were enrolled and categorized into three groups: a PD-1/PD-L1 inhibitor combined with chemotherapy group (n = 35), a tyrosine kinase inhibitor group (n = 36), and a PRaG therapy group (n = 30). Clinical outcomes, including median progression-free survival (mPFS), median overall survival (mOS), response rates, and prognostic factors, were analyzed using SPSS 26.0. The prognostic analyses being conducted only in the PRaG therapy group. PRaG therapy group had the highest objective response rate (20.0%) and the longest mPFS (4.5 months, P < 0.05). However, no significant difference in mOS was observed among the groups. Prognostic analysis identified baseline peripheral lymphocyte counts, CD8 + T cell counts, and IL-17A levels as independent factors influencing treatment outcomes. CONCLUSIONS: PD-1/PD-L1 inhibitor-based therapies show clinical efficacy in MSS/pMMR mCRC patients. PRaG therapy has potential advantages over chemotherapy or tyrosine kinase inhibitors, with CD8 + T cell counts and IL-17A levels being key prognostic markers.