Clinical Summary: 

• Design/Population: In this phase 3 trial, patients with recurrent or metastatic head and neck squamous cell carcinoma were randomly assigned to receive platinum-based chemotherapy or triple oral metronomic chemotherapy combined with ultra-low-dose nivolumab.
• Key Outcomes: Triple oral metronomic chemotherapy plus immunotherapy significantly improved overall survival, progression-free survival, and response rates compared with platinum-based chemotherapy while reducing severe toxicity.
• Clinical Relevance: These findings support a low-cost, accessible chemo-immunotherapy regimen as a potential first-line treatment option, particularly in resource-limited settings.

Results from a phase 3 trial showed that triple oral metronomic chemotherapy combined with ultra-low-dose nivolumab demonstrates clinical promise among patients with recurrent or metastatic head and neck squamous cell carcinoma.

These results were presented by Minit Jalan Shah, DM, Tata Memorial Hospital, Mumbai, Maharashtra, India, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this open-label, multicenter phase 3 study, 422 patients were randomized 1:1 to receive either 175 mg/m² of paclitaxel plus carboplatin AUC 6 every 3 weeks or a metronomic chemo-immunotherapy regimen consisting of 9 mg/m² of methotrexate weekly, 200 mg of celecoxib twice daily, 150 mg of erlotinib once daily, and 20 mg of nivolumab intravenously every 3 weeks. Treatment continued until disease progression or unacceptable toxicity. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS), objective response rate (ORR), safety, and quality of life.

At analysis, median OS was 10.3 months in the metronomic chemo-immunotherapy arm and 6.2 months in the platinum-based chemotherapy arm (hazard ratio [HR], 0.565; 95% confidence interval [CI], 0.439 to 0.728; P < .001), with 12-month OS rates of 46% and 23% and 6-month OS rates of 69% and 52, respectively. Median PFS was 5.5 months in the metronomic chemo-immunotherapy arm and 2.7 months in the platinum-based chemotherapy arm (HR, 0.465; 95% CI, 0.371 to 0.582; P < .001). Median ORR was 53.4% and 24.1%, respectively (P < .001). 

Grade ≥3 adverse events were reported in 34.1% of patients in the metronomic chemo-immunotherapy arm and 46.4% of patients in the  platinum-based chemotherapy (P = .010). No treatment-related deaths were reported, and patient-reported quality of life was maintained with the metronomic regimen.

“[Triple oral metronomic chemotherapy combined with ultra-low-dose immunotherapy] represents a promising and cost-effective first-line treatment option,” concluded Dr Shah. 

Source: 

Shah MJ, Noronha V, Menon NS, et al. Ultra-low-dose immunotherapy plus oral metronomic chemotherapy versus paclitaxel-carboplatin in platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma: A randomized phase III trial. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA6007.