55P Time to combine? A predictive modeling study of combination systemic therapies in patients with salivary gland cancers based on phase II clinical trials

Background: Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).Previous studies suggest that ICIs may enhance not only first-line outcomes but also the effectiveness of subsequent therapies; however, the heterogeneity of post-ICI treatments has not been adequately evaluated.Thus, it remains unclear whether prior ICI exposure truly influences the efficacy of subsequent chemotherapy.This study aimed to assess whether prior ICI exposure improves the outcomes of paclitaxel plus cetuximab (PC). Methods:We retrospectively reviewed 180 patients with R/M HNSCC who received PC at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between March 2013 and October 2025.Patients were categorized into the prior-ICI group or the ICI-naive group.The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and objective response rate (ORR).Survival outcomes were analyzed using Kaplan-Meier estimates and Cox proportional hazards models.Variables with p < 0.05 in univariate Cox analysis were included in multivariate modeling.The study was approved by the institutional review board (2023-GB-076).Results: Among 178 eligible patients, 63 (35.4%) were in the prior-ICI group and 115 (64.6%) were in the ICI-naive group.Median PFS was 8.1 months in the prior-ICI group and 5.3 months in the ICI-naive group (p < 0.01).Median OS was 13.6 vs 11.1 months, respectively (p < 0.01).ORR was higher in the prior-ICI group (55.2% vs 31.8%,p < 0.01).In univariate analysis, prior ICI exposure significantly improved PFS (HR 0.55; 95% CI 0.39-0.77;p < 0.01) and OS (HR 0.62; 95% CI 0.43-0.91;p < 0.01).In multivariate analysis, prior ICI exposure remained an independent favorable factor for PFS (HR 0.58; 95% CI 0.39-0.85;p < 0.01) and OS (HR 0.57; 95% CI 0.38-0.86;p < 0.01). Conclusions:Prior ICI exposure significantly improved OS, PFS, and ORR in patients treated with PC.These findings clearly demonstrate that ICI administration before PC provides a survival advantage in R/M HNSCC and highlights the clinical relevance of treatment sequencing.