{"entity":{"id":"keynote-716","kind":"trial","name":"KEYNOTE-716","aka":[],"tldr":"Extended adjuvant immunotherapy to thick node-negative melanomas, a group whose risk of relapse rivals stage III.","summary":"RFS and distant metastasis-free survival improved (FDA approval December 2021 for stage IIB/IIC). Five-year follow-up (ESMO 2025) reported sustained RFS and DMFS benefit; OS not yet mature. The absolute benefit is smaller than in stage III and the trial reignited debate about over-treatment given that most stage II patients never relapse.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03553836","url":"https://clinicaltrials.gov/study/NCT03553836"},{"label":"5-year follow-up, Annals of Oncology 2025","url":"https://www.annalsofoncology.org/article/S0923-7534(25)03159-X/fulltext"}],"tags":[],"related":[],"cancers":["melanoma","stage-ii-melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["efs"],"trials":[],"people":["jason-luke"],"bottlenecks":[],"keyPapers":["paper-keynote-716-lancet-2022","paper-keynote-716-lancet-oncol-2022-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03553836","phase":"3","setting":"Resected stage IIB or IIC melanoma: adjuvant pembrolizumab 1 year vs placebo","sponsor":"Merck","result":"RFS and DMFS improved; 5-year benefit sustained (ESMO 2025).","started":"2018-09-12","startedType":"actual","yearReported":2021,"enrolled":976,"enrolledBasis":"registry","outcomes":[{"endpoint":"Recurrence-free survival (first interim analysis)","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab","n":487,"note":"Median not reached in either arm; HR 0.61 (95% CI 0.45-0.82) at the second interim analysis"},{"name":"Placebo","n":489}],"hr":0.65,"ci":[0.46,0.92],"p":"0.0066","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00562-1/fulltext"},{"endpoint":"Distant metastasis-free survival at 36 months (final DMFS analysis)","unit":"%","arms":[{"name":"Pembrolizumab","value":84.4},{"name":"Placebo","value":74.7}],"hr":0.59,"ci":[0.44,0.79],"source":"https://ascopubs.org/doi/10.1200/JCO.23.02355"},{"endpoint":"Recurrence-free survival at 36 months","unit":"%","arms":[{"name":"Pembrolizumab","value":76.2},{"name":"Placebo","value":63.4}],"hr":0.62,"ci":[0.49,0.79],"source":"https://ascopubs.org/doi/10.1200/JCO.23.02355"},{"endpoint":"Recurrence-free survival at 48 months","unit":"%","arms":[{"name":"Pembrolizumab","value":71.3},{"name":"Placebo","value":58.3}],"hr":0.62,"ci":[0.5,0.78],"source":"https://doi.org/10.1016/j.ejca.2025.115381"}],"replication":"Consistent with the stage III adjuvant trials (KEYNOTE-054, CheckMate 238) and with CheckMate 76K (nivolumab in stage IIB/C, RFS HR 0.42), so adjuvant PD-1 benefit in stage II is replicated across two agents. OS not yet significant."},"route":"/trials/keynote-716/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"stage-ii-melanoma","kind":"cancer","name":"Stage IIB and IIC melanoma","route":"/cancers/stage-ii-melanoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"}],"person":[{"id":"jason-luke","kind":"person","name":"Jason J. Luke","route":"/people/jason-luke/"}],"paper":[{"id":"paper-keynote-716-lancet-2022","kind":"paper","name":"KEYNOTE-716: adjuvant pembrolizumab versus placebo in completely resected stage IIB or IIC melanoma","route":"/key-papers/paper-keynote-716-lancet-2022/"},{"id":"paper-keynote-716-lancet-oncol-2022-update","kind":"paper","name":"Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial","route":"/key-papers/paper-keynote-716-lancet-oncol-2022-update/"}],"idea":[{"id":"idea-ctdna-guided-adjuvant-melanoma","kind":"idea","name":"ctDNA-guided adjuvant therapy in stage II-III melanoma","route":"/ideas/idea-ctdna-guided-adjuvant-melanoma/"}]}}