{"entity":{"id":"idea-reg-antihistamine-plus-io-trial","kind":"idea","name":"Randomise a cheap antihistamine alongside immunotherapy","aka":[],"tldr":"Patients who happened to take common allergy pills during immunotherapy seemed to live longer in a large records study. A simple randomised trial would show whether the pills really help.","summary":"A 2022 analysis of MD Anderson records (Li and colleagues, Cancer Cell) found that H1-antihistamine use during checkpoint inhibitor therapy was associated with improved survival in melanoma and lung cancer, with mechanistic work suggesting histamine-HRH1 signalling in macrophages drives T-cell dysfunction. Antihistamines cost pennies and are extremely safe. The proposal is a placebo-controlled randomised trial of a non-sedating H1-antihistamine (for example fexofenadine or loratadine) added to standard checkpoint inhibitor therapy in non-small cell lung cancer, with a plasma histamine biomarker sub-study.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No incentive to repurpose cheap drugs): Pantziarka et al., The Repurposing Drugs in Oncology (ReDO) Project (ecancer 2014)","url":"https://doi.org/10.3332/ecancer.2014.442"}],"tags":[],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":["md-anderson"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-generic-repurposing","b-immunotherapy-response"],"keyPapers":["paper-keynote-189-nejm-2018","paper-pantziarka-ecancermedicalscience"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Adding an H1-antihistamine to first-line checkpoint inhibitor therapy improves progression-free survival with a hazard ratio of 0.8 or better, with the effect concentrated in patients with high plasma histamine.","rationale":"The observational effect size was large, a mechanism has been demonstrated in mice, and the intervention has essentially no cost or toxicity, making the expected value of a trial very high even at modest prior probability.","test":"Phase 2/3 randomised double-blind trial of roughly 600 patients with NSCLC starting pembrolizumab-based therapy, PFS primary endpoint, biomarker-stratified analysis.","maturity":"preclinical-evidence","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-reg-antihistamine-plus-io-trial/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"bottleneck":[{"id":"b-generic-repurposing","kind":"bottleneck","name":"No incentive to repurpose cheap drugs","route":"/bottlenecks/b-generic-repurposing/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","route":"/key-papers/paper-keynote-189-nejm-2018/"},{"id":"paper-pantziarka-ecancermedicalscience","kind":"paper","name":"The Repurposing Drugs in Oncology (ReDO) Project","route":"/key-papers/paper-pantziarka-ecancermedicalscience/"}]}}