{"entity":{"id":"paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015","kind":"paper","name":"KEYNOTE-006 (Robert 2015): pembrolizumab versus ipilimumab in advanced melanoma","aka":[],"tldr":"Head to head, the PD-1 antibody pembrolizumab held melanoma back longer, prolonged life and caused fewer severe side effects than ipilimumab, the CTLA-4 antibody that had been the first immunotherapy to extend survival.","summary":"KEYNOTE-006 randomised 834 patients with advanced melanoma, most untreated with immunotherapy, to pembrolizumab every two weeks, pembrolizumab every three weeks, or ipilimumab. Both pembrolizumab schedules improved progression-free and overall survival and roughly tripled the response rate compared with ipilimumab, with fewer grade 3 to 5 treatment-related adverse events. The trial made PD-1 blockade the first-line immunotherapy standard in melanoma and showed the three-weekly schedule was as effective as the two-weekly one.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1503093"},{"label":"ClinicalTrials.gov NCT01866319","url":"https://clinicaltrials.gov/study/NCT01866319"}],"tags":[],"related":["paper-hodi-ipilimumab-melanoma-nejm-2010"],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":["pd1","ctla4"],"drugs":["pembrolizumab","ipilimumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["pfs","os","orr"],"trials":["keynote-006"],"people":["caroline-robert"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1503093","authors":"Robert C, Schachter J, Long GV, et al.","paperType":"rct","findings":["834 patients with advanced melanoma; pembrolizumab every 2 weeks, every 3 weeks, or ipilimumab.","Six-month progression-free survival 47.3% and 46.4% vs 26.5%; hazard ratios 0.58.","Twelve-month overall survival 74.1% and 68.4% vs 58.2%; hazard ratios 0.63 and 0.69.","Response rates 33.7% and 32.9% vs 11.9%; grade 3 to 5 treatment-related adverse events 13.3% and 10.1% vs 19.9%."],"whatItMeans":"This trial settled which checkpoint to block first in melanoma and set the pattern for PD-1 antibodies displacing ipilimumab across cancers. Long-term follow-up later showed that many responders remained free of progression years after stopping treatment.","caveats":["Open-label design.","Ipilimumab was given at 3 mg/kg for four doses; the comparison does not cover combination therapy.","Most patients had received no prior systemic therapy, so results apply mainly to first-line use."],"changedPractice":true,"participants":834},"route":"/key-papers/paper-keynote-006-pembrolizumab-ipilimumab-melanoma-nejm-2015/","neighbours":{"paper":[{"id":"paper-hodi-ipilimumab-melanoma-nejm-2010","kind":"paper","name":"Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma","route":"/key-papers/paper-hodi-ipilimumab-melanoma-nejm-2010/"}],"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"target":[{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pfs","kind":"term","name":"Progression-free survival (PFS)","route":"/terms/pfs/"}],"trial":[{"id":"keynote-006","kind":"trial","name":"KEYNOTE-006","route":"/trials/keynote-006/"}],"person":[{"id":"caroline-robert","kind":"person","name":"Caroline Robert","route":"/people/caroline-robert/"}],"idea":[{"id":"idea-bio2-lymph-node-immune-priming","kind":"idea","name":"Treat the draining lymph node before removing it","route":"/ideas/idea-bio2-lymph-node-immune-priming/"}]}}