Low-Dose Immunotherapy in Head and Neck Cancer: A Randomized Study

Abstract

PURPOSE The regimens approved for the treatment of advanced head and neck squamous cell carcinoma are accessible to only 1%-3% of patients in low- and middle-income countries because of their cost. In our previous study, metronomic chemotherapy improved survival in this setting. Retrospective data suggest that a low dose of nivolumab may be efficacious. Hence, we aimed to assess whether the addition of low-dose nivolumab to triple metronomic chemotherapy (TMC) improved overall survival (OS). METHODS This was a randomized phase III superiority study. Adult patients with recurrent or newly diagnosed advanced head and neck squamous cell carcinoma being treated with palliative intent with an Eastern Cooperative Oncology Group performance status of 0-1 were eligible. Patients were randomly assigned 1:1 to TMC consisting of oral methotrexate 9 mg/m2 once a week, celecoxib 200 mg twice daily, and erlotinib 150 mg once daily, or TMC with intravenous nivolumab (TMC-I) 20 mg flat dose once every 3 weeks. The primary end point was 1-year OS. RESULTS One hundred fifty-one patients were randomly assigned, 75 in TMC and 76 in the TMC-I arm. The addition of low-dose nivolumab led to an improvement in the 1-year OS from 16.3% (95% CI, 8.0 to 27.4) to 43.4% (95% CI, 30.8 to 55.3; hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036). The median OS in TMC and TMC-I arms was 6.7 months (95% CI, 5.8 to 8.1) and 10.1 months (95% CI, 7.4 to 12.6), respectively ( P = .0052). The rate of grade 3 and above adverse events was 50% and 46.1% in TMC and TMC-I arms, respectively ( P = .744). CONCLUSION To our knowledge, this is the first-ever randomized study to demonstrate that the addition of low-dose nivolumab to metronomic chemotherapy improved OS and is an alternative standard of care for those who cannot access full-dose checkpoint inhibitors.

Low-Dose Immunotherapy Plus Triple Metronomic Chemotherapy for Head and Neck Cancer

“…We have read the recent article published in the Journal of Clinical Oncology by Patil et al, 1 who reported that compared with triple metronomic chemotherapy (TMC, consisting of capsule celecoxib 200 mg twice daily, weekly methotrexate 9 mg/m 2 once a week, and erlotinib 150 mg once daily), the addition of low-dose nivolumab (20 mg flat dose intravenously once every 3 weeks) to TMC (TMC-I) was associated with significantly improved overall survival (OS) in the treatment of advanced head and neck squamous cell carcinoma (HNSCC). The median OS for TMC and TMC-I was 6.7 and 10.1 months, respectively (hazard ratio, 0.545; 95% CI, 0.362 to 0.820; P = .0036).…”

Highlights from the Choosing Wisely 2022 for Resource Limited Settings: Reducing Low Value Cancer Care for Sustainability conference, 17th–18th September, Mumbai, India

“…He suggested strategies such as using lower dose or less frequent dosing (immunotherapy drugs), shorter duration of treatment (6 months of adjuvant trastuzumab instead of 1 year), dose modifiers including food (abiraterone) and therapeutic substitution (use of generics, wherever approved) [ 4 ]. Dr Tannock applauded the conduct of low-dose immunotherapy trials in India (the use of low-dose, 20 mg nivolumab for palliation of head and neck cancer in TMH by Dr Vijay Patil has shown significant improvement in overall survival compared to chemotherapy) [ 5 ].…”

Cost Savings and Increased Access With Ultra-Low-Dose Immunotherapy

“…In the article that accompanies this editorial, Patil et al 1 reported findings from a randomized clinical trial of nivolumab for advanced head and neck cancer. This trial found a substantial overall survival benefit from the addition of nivolumab to a regimen combining cytotoxic (methotrexate) and targeted (erlotinib) therapies.…”