Results from a new study out of India found that triple oral metronomic chemotherapy combined with ultra-low-dose immunotherapy (TMC-I) could help some people with advanced head and neck squamous cell carcinoma (HNSCC) live longer with fewer side effects and at a lower cost than standard treatments.

This is especially important for patients in low- and middle-income countries who may not have access to standard treatments.

The research was presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, which took place May 29 to June 2 in Chicago. 

“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. This study demonstrates that a low-cost, well-tolerated regimen can significantly improve survival, making it highly relevant for global oncology practices,” said lead study author Minit Jalan Shah, MBBS, MD, of the Tata Memorial Centre in Mumbai, India.

This phase 3 clinical trial out of India included 422 people with platinum-sensitive advanced HNSCC treated with a palliative intent.

Among the participants, most of whom were male (85.5%) and had a median age of 49.5, about 87% had tobacco exposure, a common risk factor for HNSCC; 76.3% had cancer in the oral cavity; 25.6% had metastatic disease; and about 31% had an ECOG performance status of 2.

Together, these features represent a high-risk group of patients who typically have more aggressive cancer.

The participants were randomly assigned to receive either platinum-based chemotherapy with paclitaxel and carboplatin (211 participants) or TMC-I that included methotrexate, celecoxib, erlotinib, and nivolumab given at an ultra-low dose (211 participants).

Key Findings

• The median overall survival (OS) was 10.3 months in the TMC-I group vs. 6.2 months in the chemotherapy group. Overall, those in the TMC-I group had a 43% lower risk of death.
• At 1 year, the OS rate in the TMC-I group was double that of the chemotherapy group (46% vs. 23%).
• The survival benefit of TMC-I was consistent across subgroups, with a greater benefit seen in those with oral cavity cancer and those who used or had used tobacco.
• The TMC-I group had a higher: 
  • Overall response rate at 53.4% vs. 24.1% in the chemotherapy group. 
  • Median duration of response (DoR) of 11 months vs. 3.6 months in the chemotherapy group. At 1 year, the DoR rates were 44.5% vs. 11.6%, respectively. Those in the TMC-I group had a 68% lower risk of the cancer growing after having a response to treatment.
  • Median progression-free survival of 5.5 months vs. 2.7 months in the chemotherapy group. Those in the TMC-I group had a 53% lower risk of disease progression or death.

Those in the TMC-I group experienced fewer serious side effects, with 37.1% of participants experiencing a grade 3 or higher adverse event vs. 47.5% of those in the chemotherapy group.

The most common side effects in the chemotherapy group were blood related, while the most common side effects in the TMC-I group were elevated liver enzymes (8.9% of participants), excess bilirubin (4.5%), and rash (8.4%).

“This study is important in that it represents a potential therapy option for patients in resource-limited parts of the world, including India, where the research was conducted. The median overall survival was improved in the triple oral metronomic chemotherapy combined with ultra-low-dose immunotherapy arm when compared with chemotherapy. However, the comparator regimen would not be a standard first-line option in the U.S., and the overall survival is lower than what we observe with standard first-line U.S. agents,” said Glenn J. Hanna, MD, Director of the Center for Cancer Therapeutic Innovation at Dana-Farber Cancer Institute and an ASCO Expert in head and neck cancers.

The researchers plan to evaluate combination strategies that incorporate both intravenous chemotherapy and TMC-I, and they’re aiming to identify genomic and molecular predictors of response to help personalize treatment.

They also plan to explore treatment adaptation strategies, including escalation or de-escalation of the intensity of the treatment drugs based on response and liquid biopsy findings, and study this approach in earlier disease settings.

Source: ASCO