According to findings from a phase III trial presented at the 2026 ASCO Annual Meeting (Abstract LBA6007), a low-cost regimen combining triple oral metronomic chemotherapy with ultra-low-dose immunotherapy significantly improved survival and reduced toxicity compared with platinum-based chemotherapy in patients with platinum-sensitive advanced head and neck squamous cell carcinoma (HNSCC).
Study Details
The study enrolled 422 patients in India with advanced HNSCC being treated with palliative intent. Participants were randomly assigned to receive either paclitaxel plus carboplatin chemotherapy (n = 211) or a regimen designated TMC-I consisting of methotrexate, celecoxib, erlotinib, and ultra-low-dose nivolumab (n = 211). Most patients were male (85.5%), had a history of tobacco exposure (approximately 87%), and had oral cavity primary tumors (76.3%), representing a population with generally poor-risk disease characteristics.
Key Results
Median overall survival, the study’s primary endpoint, was 10.3 months with TMC-I compared with 6.2 months with chemotherapy, corresponding to a 43% reduction in the risk of death. One-year overall survival rates were 46% and 23%, respectively. Investigators reported that the survival advantage was observed across patient subgroups, with particularly pronounced benefit among patients with oral cavity cancers and those with a history of tobacco use.
The experimental regimen also improved several secondary efficacy endpoints. The overall response rate was 53.4% with TMC-I vs 24.1% with chemotherapy. Median duration of response was 11 months compared with 3.6 months, and patients receiving TMC-I experienced a 68% lower risk of disease progression following an initial response. Median progression-free survival was 5.5 months with TMC-I vs 2.7 months in the chemotherapy arm, translating to a 53% reduction in the risk of disease progression or death.
Grade 3 or higher adverse events occurred in 37.1% of patients treated with TMC-I vs 47.5% of those receiving chemotherapy. Hematologic toxicities predominated in the chemotherapy arm, whereas the most common adverse events in the TMC-I group included elevated liver enzymes, hyperbilirubinemia, and rash.
The investigators emphasized the global health implications of the findings. Current first-line treatment approaches for advanced HNSCC often combine platinum-based chemotherapy with immunotherapy or targeted therapy, but these regimens may be prohibitively expensive in many low- and middle-income countries. According to the study authors, standard treatment can exceed $1,000 per month, whereas the TMC-I regimen costs approximately $230 monthly.
“Although effective treatments such as immunotherapy and cetuximab exist for patients with advanced head and neck cancer, they remain inaccessible to most patients due to cost and toxicity,” said lead author Minit Jalan Shah, MBBS, MD, of Tata Memorial Centre in Mumbai. “This study demonstrates that a low-cost, well-tolerated regimen can significantly improve survival, making it highly relevant for global oncology practices.”
Glenn J. Hanna, MD, of Dana-Farber Cancer Institute and an ASCO Expert in head and neck cancer, noted that the findings may be particularly relevant in resource-constrained settings, while cautioning that the chemotherapy comparator used in the trial “would not be a standard first-line option in the U.S.” and that survival outcomes were lower than those typically observed with contemporary U.S. first-line therapies.
DISCLOSURE: For full disclosures of the study authors, visit coi.asco.org.
