HEAD and neck cancer survival improved significantly with ultra-low-dose immunotherapy plus oral metronomic chemotherapy compared with paclitaxel and carboplatin in patients receiving first-line palliative therapy for recurrent or metastatic head and neck squamous cell carcinoma, according to randomized Phase III results presented at ASCO.
Head And Neck Cancer Survival Improves With TMC-I
The open-label, multicenter trial randomized 422 patients with recurrent or metastatic head and neck squamous cell carcinoma to paclitaxel 175 mg/m² plus carboplatin AUC 6 every 3 weeks or TMC-I, comprising oral methotrexate 9 mg/m² weekly, celecoxib 200 mg twice daily, erlotinib 150 mg daily, and nivolumab 20 mg IV every 3 weeks. Treatment continued until disease progression or unacceptable toxicity.
The study population reflected a clinically challenging cohort. Median age was 49.5 years, 85.5% of patients were male, 78.9% reported oral tobacco use, and 76.3% had oral cavity primary tumors. Metastatic disease was present in 25.6%, while 30.6% had ECOG performance status 2.
TMC-I met the primary endpoint of overall survival. Median overall survival reached 10.3 months with TMC-I compared with 6.2 months with paclitaxel and carboplatin, representing a 44% reduction in the risk of death. Twelve-month overall survival was 46% with TMC-I versus 23% with platinum-based chemotherapy, while six-month overall survival was 69% versus 52%.
Response And Safety Favor Oral Metronomic Chemotherapy Approach
Disease control also favored the head and neck cancer regimen. Median progression-free survival was 5.5 months with TMC-I versus 2.7 months with paclitaxel and carboplatin. Objective response rates were more than doubled, at 53.4% versus 24.1%.
Safety findings further supported the investigational regimen. Grade 3 or higher adverse events occurred in 34.1% of patients receiving TMC-I compared with 46.4% receiving platinum-based chemotherapy. No treatment-related deaths were observed, and patient-reported quality of life was preserved with TMC-I.
The findings suggest that ultra-low-dose immunotherapy plus oral metronomic chemotherapy may offer a practical first-line option for recurrent or metastatic head and neck squamous cell carcinoma, particularly in settings where standard pembrolizumab- or cetuximab-containing regimens remain difficult to access. At approximately USD 230 per month, TMC-I was presented as a promising cost-conscious strategy with clinically meaningful survival, response, tolerability, and quality-of-life advantages.
Reference
Shah MJ 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. Abstract LBA6007. ASCO Annual Meeting, 2026.
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