{"entity":{"id":"keynote-a18","kind":"trial","name":"KEYNOTE-A18 / ENGOT-cx11 / GOG-3047","aka":[],"tldr":"Adding immunotherapy to curative chemoradiation for locally advanced cervical cancer improved both control and survival, the first such advance in two decades.","summary":"KEYNOTE-A18, also ENGOT-cx11 and GOG-3047, trial NCT04221945 sponsored by Merck and published in the Lancet in 2024, showed that adding pembrolizumab to curative cisplatin chemoradiation and brachytherapy for high-risk locally advanced cervical cancer improves both disease control and survival, the first such advance in two decades. It randomised 1,060 patients, met its primary progression-free survival endpoint at 24 months and its overall survival endpoint at 36 months, and led to FDA approval in January 2024 for FIGO 2014 stage III to IVA disease, the first change to the cisplatin-radiation standard set in 1999. CALLA with durvalumab was negative, so the benefit is not yet reproduced with another agent, and why the two trials diverged is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04221945","url":"https://clinicaltrials.gov/study/NCT04221945"},{"label":"PFS, Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)00317-9"},{"label":"OS, Lancet 2024","url":"https://doi.org/10.1016/S0140-6736(24)01808-7"}],"tags":[],"related":[],"cancers":["cervical","locally-advanced-cervical-cancer"],"sections":[],"technologies":["imrt-igrt","brachytherapy","checkpoint-inhibitor"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["gog-foundation"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["domenica-lorusso","bradley-monk"],"bottlenecks":[],"keyPapers":["paper-keynote-a18-pfs-lancet-2024","paper-keynote-a18-os-lancet-2024"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04221945","phase":"3","setting":"Newly diagnosed high-risk locally advanced cervical cancer (FIGO 2014 IB2-IIB node-positive or III-IVA): pembrolizumab + cisplatin chemoradiation + brachytherapy, then pembrolizumab, vs chemoradiation","sponsor":"Merck","result":"PFS HR 0.70; 36-month OS 82.6% vs 74.8% (HR 0.67).","started":"2020-05-12","startedType":"actual","yearReported":2023,"enrolled":1060,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival at 24 months","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + CRT","n":529,"value":68},{"name":"Placebo + CRT","n":531,"value":57}],"hr":0.7,"ci":[0.55,0.89],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00317-9/fulltext"},{"endpoint":"Overall survival at 36 months","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + CRT","value":82.6},{"name":"Placebo + CRT","value":74.8}],"hr":0.67,"ci":[0.5,0.9],"source":"https://pubmed.ncbi.nlm.nih.gov/39288779/"}],"replication":"CALLA (durvalumab + chemoradiation) was negative, so the benefit is not yet reproduced with another agent; differences in risk population and drug are debated."},"route":"/trials/keynote-a18/","neighbours":{"cancer":[{"id":"cervical","kind":"cancer","name":"Cervical cancer","route":"/cancers/cervical/"},{"id":"locally-advanced-cervical-cancer","kind":"cancer","name":"Locally advanced cervical cancer","route":"/cancers/locally-advanced-cervical-cancer/"},{"id":"vaginal","kind":"cancer","name":"Vaginal cancer","route":"/cancers/vaginal/"}],"technology":[{"id":"brachytherapy","kind":"technology","name":"Brachytherapy","route":"/technologies/brachytherapy/"},{"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/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"gog-foundation","kind":"company","name":"GOG Foundation","route":"/companies/gog-foundation/"}],"person":[{"id":"bradley-monk","kind":"person","name":"Bradley J. Monk","route":"/people/bradley-monk/"},{"id":"domenica-lorusso","kind":"person","name":"Domenica Lorusso","route":"/people/domenica-lorusso/"}],"paper":[{"id":"paper-keynote-a18-os-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)","route":"/key-papers/paper-keynote-a18-os-lancet-2024/"},{"id":"paper-keynote-a18-pfs-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (progression-free survival)","route":"/key-papers/paper-keynote-a18-pfs-lancet-2024/"}],"pairing":[{"id":"io-plus-crt-cervical","kind":"pairing","name":"PD-1 blockade + chemoradiation (locally advanced cervical cancer)","route":"/pairings/io-plus-crt-cervical/"}],"idea":[{"id":"idea-tr1-low-dose-immunotherapy-for-lmic","kind":"idea","name":"Confirm ultra-low-dose immunotherapy so it can be afforded where most patients live","route":"/ideas/idea-tr1-low-dose-immunotherapy-for-lmic/"},{"id":"idea-hpv-ctdna-cervical","kind":"idea","name":"HPV circulating tumour DNA to guide cervical cancer therapy","route":"/ideas/idea-hpv-ctdna-cervical/"}],"institution":[{"id":"sgo","kind":"institution","name":"Society of Gynecologic Oncology","route":"/institutions/sgo/"}],"roadmap":[{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"}]}}