A Real‐World Phase IV Superiority Trial and Cost‐Effectiveness Analysis of the Addition of Low‐Dose Nivolumab to Triple Metronomic Chemotherapy Compared to the Paclitaxel Carboplatin Regimen in Recurrent or Metastatic Head and Neck Cancer Patients

ABSTRACT Background Limited data are available regarding the comparison of low‐dose immunotherapy when added to oral metronomic chemotherapy with conventional induction chemotherapy regimens in recurrent/metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC). Methods This real‐world phase IV superiority trial recruited adult patients with R/M HNSCC being treated with palliative intent. Patients were assigned to TMC‐I or PC. The primary endpoints were median OS, PFS, ORR, and ICER, and the safety assessment was the secondary endpoint. Results A total of 154 patients were recruited: 78 in the TMC‐I arm and 76 in the PC arm. The median OS was 15.13 months (95% CI, 11.05–19.20) versus 9.8 months (95% CI, 7.50–12.09) ( p < 0.01), and the median PFS was 11.20 months (95% CI, 5.43–16.96) versus 7.41 months (95% CI, 6.73–8.08) ( p < 0.01) for the TMC‐I and PC arms, respectively. The ORR was 69.23% for TMC‐I and 31.57% for the PC arm, respectively. The ICER between both arms was 68 947. Conclusion A significant improvement in survival, tolerability, and reasonable cost‐effectiveness was observed with low‐dose immunotherapy when added to oral metronomic chemotherapy compared to conventional chemotherapy regimens.