Outcomes and toxicities of triple metronomic chemotherapy with low-dose nivolumab and axitinib in unresectable, recurrent, and metastatic head-and-neck squamous cell carcinomas: A real-world retrospective analysis from a resource-constrained setting

ABSTRACT Background: This study aimed to evaluate whether the addition of an anti-vascular endothelial growth factor (VEGF) agent, axitinib, to oral metronomic chemotherapy and low-dose nivolumab could improve survival outcomes without increasing toxicities in patients with advanced, unresectable, or metastatic head-and-neck squamous cell carcinoma (HNSCC). Objectives: The primary objective was to assess overall survival (OS) with the addition of axitinib to triple metronomic chemotherapy and low-dose nivolumab in advanced, unresectable, recurrent, or metastatic HNSCC. Secondary objectives included progression-free survival (PFS), overall response rate (ORR), and adverse event (AE) assessment. Material and Methods: This retrospective study included 167 patients treated at the Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, between April 2022 and May 2024. Patients received oral metronomic chemotherapy (methotrexate, erlotinib, and celecoxib), axitinib, and low-dose nivolumab. OS and PFS were estimated using the Kaplan–Meier method, and AEs were graded as per CTCAE version 5.0. Results: The median OS was 7 months (95% confidence interval [CI]: 5.5–8.5), and the median PFS was 6.7 months (95% CI: 4.9–8.4). The ORR was 38%, including complete responses in nine patients. Grade ≥ 3 AEs occurred in 65.2% ( n = 86), most commonly skin rash (18.2%, n = 24), hyponatremia (10.6%, n = 14), and transaminitis (9.8%, n = 13). Treatment-related toxicities led to dose interruptions or modifications in 36% ( n = 48). Conclusion: The addition of axitinib to triple metronomic chemotherapy and low-dose nivolumab increased the rate of high-grade toxicities without demonstrating improvement in survival outcomes.