{"entity":{"id":"paper-patil-low-dose-nivolumab-jco-2023","kind":"paper","name":"Low-dose immunotherapy in head and neck cancer: a randomised study (Tata Memorial)","aka":[],"tldr":"Giving about one-twentieth of the standard dose of nivolumab alongside cheap oral chemotherapy nearly tripled one-year survival in advanced head and neck cancer, showing that immunotherapy can be made affordable without losing its effect.","summary":"Open-label phase 3 randomising 151 patients with advanced head and neck squamous cell carcinoma being treated with palliative intent to triple oral metronomic chemotherapy with or without nivolumab 20 mg flat every 3 weeks. One-year overall survival was 43.4% (95% CI 30.8-55.3) with nivolumab versus 16.3% (8.0-27.4) without; median overall survival 10.1 versus 6.7 months (hazard ratio 0.545; 95% CI 0.362-0.820; P=0.0036); grade 3 or worse adverse events 46.1% versus 50%.\n\nThe dose is roughly 6% of the approved flat dose and the drug cost correspondingly small. The trial has become the reference case for dose-optimisation in immuno-oncology and for pragmatic trials in low- and middle-income countries.","asOf":"2026-09-10","links":[{"label":"JCO 2023","url":"https://doi.org/10.1200/JCO.22.01015"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["nivolumab"],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":[],"trials":["low-dose-nivolumab-tmh"],"people":["patil-vijay","prabhash-kumar","noronha-vanita"],"bottlenecks":["b-dose-optimisation","b-drug-pricing"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2023,"doi":"10.1200/JCO.22.01015","authors":"Patil VM, Noronha V, Menon N, et al.","paperType":"rct","findings":["One-year overall survival 43.4% with low-dose nivolumab versus 16.3% without.","Median overall survival 10.1 versus 6.7 months; hazard ratio 0.545 (95% CI 0.362-0.820).","No increase in grade 3 or worse adverse events (46.1% versus 50%).","Nivolumab dose was a flat 20 mg every 3 weeks, a small fraction of the licensed dose."],"whatItMeans":"For the majority of the world's head and neck cancer patients who cannot afford full-dose checkpoint inhibitors, a low dose added to oral metronomic chemotherapy is a tested alternative that improves survival. It also challenges the assumption that approved doses are the necessary doses: pharmacology had long suggested receptor saturation at far lower exposures.","caveats":["Single-centre and open-label; the comparator was metronomic chemotherapy rather than the standard-dose immunotherapy used in high-income settings.","Whether low-dose nivolumab matches full-dose nivolumab head to head is untested.","Patients were mostly tobacco-related, HPV-negative oral cancers, so applicability to oropharyngeal HPV-positive disease is unknown."],"changedPractice":true,"participants":151},"route":"/key-papers/paper-patil-low-dose-nivolumab-jco-2023/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"institution":[{"id":"tata-memorial","kind":"institution","name":"Tata Memorial Centre","route":"/institutions/tata-memorial/"}],"trial":[{"id":"low-dose-nivolumab-tmh","kind":"trial","name":"Low-dose nivolumab plus metronomic chemotherapy (Tata Memorial)","route":"/trials/low-dose-nivolumab-tmh/"}],"person":[{"id":"prabhash-kumar","kind":"person","name":"Kumar Prabhash","route":"/people/prabhash-kumar/"},{"id":"noronha-vanita","kind":"person","name":"Vanita Noronha","route":"/people/noronha-vanita/"},{"id":"patil-vijay","kind":"person","name":"Vijay Patil","route":"/people/patil-vijay/"}],"bottleneck":[{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"roadmap":[{"id":"global-access-roadmap","kind":"roadmap","name":"Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation","route":"/roadmaps/global-access-roadmap/"}]}}