Efficacy and safety of triple oral metronomic chemotherapy in patients with advanced esophageal squamous cell carcinoma.

e16043 Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) have dismal survival outcomes post-progression on standard first-line chemoimmunotherapy. The median overall survival (OS) is usually less than a year. Patients receiving subsequent line treatment options experience significant treatment related toxicities (> 50-60% develop > grade 3 toxicities), are frail, and have a poor ECOG Performance Status (> 30% have ECOG-PS >2). Triple oral metronomic chemotherapy (triple-OMCT) is an efficacious and cost-effective treatment option in patients with locally advanced head and neck SCC. We aimed to explore the role of triple-OMCT in patients of advanced ESCC treated at our institute. Methods: This was a retrospective observational study conducted at our institute between 28.05.2019 to 09.01.2025 Patients of advanced esophageal SCC who had progressed on prior lines of systemic treatment were treated with triple-OMCT (tablet methotrexate 9mg/m 2 per week, tablet erlotinib 150mg once daily, capsule celecoxib 200mg twice daily). The addition of immunotherapy was permitted with this regimen. We assessed treatment efficacy [objective response rate (ORR)], safety, and survival outcomes [progression-free (PFS), OS] in these patients. Results: The data of 57 consecutively evaluated patients was analyzed. Median age was 59 years (IQR, 52.5-63.0), 54.4% (n = 31) were females, and 86.0% (n = 49) had an ECOG-PS of 0-1. Prior treatment in the curative or palliative setting was received by 64.9% (n = 37) patients, and the median number of prior lines of treatment was 2 (IQR, 1-2). At OMCT initiation, 68.4% (n = 39) patients had metastatic disease, with 54.4% (n = 31) patients having metastasis to non-regional lymph nodes. Immunotherapy was added to triple-OMCT in 47.4% (n = 27) patients. Amongst response evaluable patients (59.6%, n = 34/57), the objective response was 14.7% (five partial response), and disease control rate was 47.1% (n = 16/34, eleven stable disease). > Grade 3 toxicity was seen in 17.5% (n = 10) patients. Median follow-up of the cohort was 28.8 months (95%CI, 18.7-39.1). The median PFS and OS with the use of triple-OMCT was 3.4 months (95%CI, 2.8-3.9) and 9.7 months (95%CI, 6.6-12.8) respectively. With the addition of immunotherapy, the median PFS and OS was 3.4 months (95%CI, 2.4–4.5) and 11.4 months (95%CI, 8.8-14.0) respectively, compared to 3.0 months (95%CI, 2.5-3.6, p = 0.618) and 7.6 months (95%CI, 4.1-11.2, p = 0.386) without immunotherapy. Conclusions: Triple-OMCT is safe and has activity in patients with advanced esophageal SCC. This regimen is worthy of exploration in resource-limited settings. Best Overall Response, n (%) Patients, n (%)N=34 Complete Response (CR) 0 (0.0) Partial Response (PR) 5 (14.7) Stable Disease (SD) 11 (32.3) Progressive Disease (PD) 18 (52.9) Objective Response Rate (ORR) 14.7% Disease Control Rate (DCR) 47.1%