{"entity":{"id":"io-before-surgery-hnscc","kind":"pairing","name":"Immunotherapy before surgery rather than with chemoradiation (HNSCC)","aka":[],"tldr":"In head and neck cancer, immunotherapy works when given before surgery but not when given alongside chemoradiation.","summary":"This sequence rule in head and neck squamous cell carcinoma places immune checkpoint inhibitors before surgery rather than concurrently with modern external beam chemoradiation. T-cell priming needs an intact tumour and functioning lymphatics, and chemoradiation destroys both while the drug is on board; radiation-induced lymphopenia, steroids and loss of the antigen-rich primary are the proposed explanations. KEYNOTE-689, which gave pembrolizumab before and after surgery, improved event-free survival, whereas JAVELIN Head and Neck 100 and KEYNOTE-412, which gave it with chemoradiation, both failed. One positive phase 3 against two negative ones makes timing, not the drug, the lesson; the concept sits under neoadjuvant, adjuvant and perioperative therapy.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03765918: KEYNOTE-689","url":"https://clinicaltrials.gov/study/NCT03765918"},{"label":"ClinicalTrials.gov NCT02952586: JAVELIN Head and Neck 100","url":"https://clinicaltrials.gov/study/NCT02952586"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant"],"trials":["keynote-689","javelin-hn-100"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"checkpoint-inhibitor","b":"imrt-igrt","rationale":"T-cell priming needs an intact tumour and functioning lymphatics; chemoradiation destroys both while the drug is on board.","evidence":"One positive phase 3 versus two negative ones with the alternative sequence.","pairingType":"sequence"},"route":"/pairings/io-before-surgery-hnscc/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"trial":[{"id":"javelin-hn-100","kind":"trial","name":"JAVELIN Head and Neck 100","route":"/trials/javelin-hn-100/"},{"id":"keynote-689","kind":"trial","name":"KEYNOTE-689","route":"/trials/keynote-689/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}]}}