Phase 3 randomized study of physician choice vs metronomic chemotherapy in platinum refractory/ineligible head and neck cancer in palliative setting with survival outcomes.

There are multiple options of treatment in second line therapy for locally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with palliative intent. However, triple metronomic chemotherapy is oral, cost-effective, and resource-efficient. Hence this phase 3 randomized trial compares National Comprehensive Cancer Network (NCCN) recommended physician choice therapy versus triple metronomic chemotherapy (TMC) in the second-line treatment of head and neck cancer This study, designed to establish superiority, was conducted in India across 16 sites under the Cancer Research Statistics Foundation. The study recruited 114 LAHNSCC who were treated with palliative intent in second line. These patients underwent 1:1 central stratified randomization to either triple metronomic chemotherapy or physician choice therapy (taxane, 5fu/capecitabine, afatinib, nivolumab/pembrolizumab, cetuximab).At a median follow-up of 258 (95 % CI 209-306) days, the median overall survival of the triple metronomic chemotherapy was 181 days (95 %CI 142.7-219.2) versus 123 days (95 %CI 94-152) in the physician choice therapy arm (P = 0.00.002). The median progression free survival was 120 days (95 %CI 89.2-150.8) versus 70 days (95 % CI 58.2-81.8) in metronomic chemotherapy and in the physician choice therapy arms respectively (P < 0.001).These results suggest that TMC significantly improves survival outcomes over physician choice therapy in platinum-refractory head and neck cancer.