Comparison of dual vs. triple oral metronomic chemotherapy using methotrexate, celecoxib with or without erlotinib in advanced head and neck squamous cell cancer: Real-world data and experience from a tertiary care center.

e18038 Background: The standard of care for unresectable or metastatic advanced head and neck squamous cell carcinoma (HNCSCC) is either immunotherapy or cetuximab-based monotherapy, or combination therapy. However, this is often unavailable to most patients due to financial constraints. Existing studies have already shown how oral metronomic therapy (OMT) outperformed other standard physician choices of chemotherapy. We aim to compare the efficacy of dual versus triple OMT in improving overall survival (OS) and progression-free survival (PFS) and to assess the factors affecting the same. Methods: This retrospective analysis, conducted after receiving approval from the AIIMS Institutional Ethics Committee, included patients diagnosed with HNCSCC who received either dual or triple metronomic chemotherapy between 2019 and 2024. They received Methotrexate 40 mg/m 2 PO weekly, Celecoxib 200 mg twice daily with or without erlotinib 150 mg daily. Palliative radiotherapy was given at the physician’s discretion(30Gy/10#). The primary endpoints were OS and PFS. Secondary endpoints included the assessment of safety and other factors affecting survival. OS and PFS were analyzed using Kaplan-Meier and log-rank tests, with hazard ratios estimated by Cox proportional hazard models. Results: In the study, out of 97 patients, 45 and 52 patients received dual and triple OMT, respectively. With a median follow-up of 10.5 months, the median OS was 5 months in the dual OMT group and 7 months in the triple OMT group (HR,0.56; 95% CI,0.33-0.93; p = 0.025). Median PFS was 2 months in the dual OMT group and 5.6 months in triple OMT (HR, 0.29; 95% CI, 0.18–0.47; p < 0.000001). Other than the regimen (dual vs triple OMT), age, sex, tumor site, receipt of prior chemotherapy, presence of metastasis, receipt of palliative radiotherapy (RT), whether de-novo or residual/recurrent disease, etc, were analyzed for their effect on OS and PFS. The addition of palliative RT significantly increased both PFS (1 vs 4 months, HR:0.4;95% CI, 0.24-0.67; p = 0.00015) and OS (4.2 months vs 7.8 months, HR:0.42,95% CI, 0.25-0.72, p value = 0.01). The sequence of RT did not affect OS or PFS. Grade 3 oral mucositis was 5.7% in the triple OMT group. and 2.7% in the dual OMT group. Only 1 patient had a Grade 3 rash with erlotinib. Conclusions: The addition of erlotinib to the dual metronomic chemotherapy regimen demonstrated a significantly improved OS and PFS and a well-tolerated toxicity profile. Palliative RT quadrupled the PFS and nearly doubled the OS in HNCSCC, even in patients with prior exposure to RT. These findings suggest a potential benefit in utilizing triple therapy in combination with palliative RT for specific subgroups of patients with HNCSCC, warranting further prospective clinical trials to validate these results.