{"entity":{"id":"paper-keynote-a18-os-lancet-2024","kind":"paper","name":"KEYNOTE-A18: pembrolizumab with chemoradiotherapy for locally advanced cervical cancer (overall survival)","aka":[],"tldr":"The second report from KEYNOTE-A18 showed that adding pembrolizumab to chemoradiotherapy for high-risk locally advanced cervical cancer also lengthened life: 82.6% of women were alive at three years against 74.8%, a third fewer deaths.","summary":"Second interim analysis of the double-blind, placebo-controlled phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial, in which 1,060 patients with newly diagnosed, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2-IIB node-positive or stage III-IVA) were randomised to pembrolizumab or placebo with cisplatin-based chemoradiotherapy followed by pembrolizumab or placebo maintenance.\n\nAt data cutoff on 8 January 2024 (median follow-up 29.9 months) median overall survival was not reached in either group; 36-month overall survival was 82.6% with pembrolizumab against 74.8% with placebo, hazard ratio for death 0.67 (p=0.0040), meeting the primary objective. Grade 3 or higher adverse events occurred in 78% and 70% of patients, and potentially immune-mediated adverse events in 39% and 17%. Together with the progression-free survival report it established immuno-chemoradiotherapy as a new standard of care for this population.","asOf":"2026-09-08","links":[{"label":"Lancet 2024 (OS)","url":"https://doi.org/10.1016/S0140-6736(24)01808-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39288779/"},{"label":"ClinicalTrials.gov NCT04221945","url":"https://clinicaltrials.gov/study/NCT04221945"}],"tags":[],"related":[],"cancers":["cervical"],"sections":[],"technologies":["checkpoint-inhibitor","imrt-igrt","brachytherapy","platinum"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":["gemelli"],"pathways":[],"terms":["pfs","os","cps","standard-of-care"],"trials":["keynote-a18"],"people":["domenica-lorusso","giovanni-scambia"],"bottlenecks":["b-global-access","b-immunotherapy-response","b-drug-pricing"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2024,"doi":"10.1016/S0140-6736(24)01808-7","pmid":"39288779","authors":"Lorusso D, Xiang Y, Hasegawa K, et al.","paperType":"rct","findings":["36-month overall survival 82.6% (95% CI 78.4-86.1) vs 74.8% (70.1-78.8); HR for death 0.67 (95% CI 0.50-0.90, p=0.0040).","Median follow-up 29.9 months; median overall survival not reached in either group.","Grade 3 or higher adverse events 78% vs 70%, most often anaemia and falls in white cell and neutrophil counts.","Potentially immune-mediated adverse events 39% vs 17%."],"whatItMeans":"The survival gain turns the earlier progression-free survival result into a clear reason to offer pembrolizumab with and after chemoradiotherapy to women with node-positive or stage III-IVA cervical cancer. Because cervical cancer is concentrated in low- and middle-income countries, the benefit reaches most women only if pricing and access follow.","caveats":["Interim analysis with median follow-up under three years; late recurrences are possible in this disease.","High-risk population only; the negative CALLA trial suggests lower-risk patients may not benefit.","About two years of pembrolizumab is costly where cervical cancer burden is highest."],"changedPractice":true,"participants":1060},"route":"/key-papers/paper-keynote-a18-os-lancet-2024/","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/"}],"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/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"institution":[{"id":"gemelli","kind":"institution","name":"Policlinico Universitario A. Gemelli","route":"/institutions/gemelli/"}],"term":[{"id":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"},{"id":"standard-of-care","kind":"term","name":"Standard of care","route":"/terms/standard-of-care/"}],"trial":[{"id":"keynote-a18","kind":"trial","name":"KEYNOTE-A18 / ENGOT-cx11 / GOG-3047","route":"/trials/keynote-a18/"}],"person":[{"id":"domenica-lorusso","kind":"person","name":"Domenica Lorusso","route":"/people/domenica-lorusso/"},{"id":"giovanni-scambia","kind":"person","name":"Giovanni Scambia","route":"/people/giovanni-scambia/"}],"bottleneck":[{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}