{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:05:00Z","timestamp":1791518700957,"version":"4.3.4"},"reference-count":30,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","award":["MO29821-UKE"],"award-info":[{"award-number":["MO29821-UKE"]}],"id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["esmoopen.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["ESMO Open"],"published-print":{"date-parts":[[2025,5]]},"DOI":"10.1016\/j.esmoop.2025.105053","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T23:45:23Z","timestamp":1746747923000},"page":"105053","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Early switch from run-in with targeted to immunotherapy in advanced BRAF-positive melanoma: final results of the randomised phase II ImmunoCobiVem trial"],"prefix":"10.1016","volume":"10","author":[{"given":"E.","family":"Livingstone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.J.","family":"Gogas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Kandolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.K.","family":"Eigentler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ziemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Terheyden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Gesierich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.A.","family":"Herbst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.C.","family":"K\u00e4hler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.C.","family":"Ziogas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017d.","family":"Miju\u0161kovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Garzarolli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Garbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Roesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ugurel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Gutzmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gaudy-Marqueste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Kiecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Utikal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Miethe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Eckhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Schadendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.esmoop.2025.105053_bib1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/S0140-6736(23)00821-8","article-title":"Cutaneous melanoma","volume":"402","author":"Long","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.esmoop.2025.105053_bib2","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1080\/0284186X.2020.1747636","article-title":"BRAF mutational status as a prognostic marker for survival in malignant melanoma: a systematic review and meta-analysis","volume":"59","author":"Ny","year":"2020","journal-title":"Acta Oncol"},{"issue":"suppl 5","key":"10.1016\/j.esmoop.2025.105053_bib3","doi-asserted-by":"crossref","first-page":"v126","DOI":"10.1093\/annonc\/mdv297","article-title":"Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"26","author":"Dummer","year":"2015","journal-title":"Ann Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib4","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1093\/annonc\/mdz411","article-title":"Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Michielin","year":"2019","journal-title":"Ann Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib5","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.annonc.2020.07.004","article-title":"ESMO consensus conference recommendations on the management of metastatic melanoma: under the auspices of the ESMO Guidelines Committee","volume":"31","author":"Keilholz","year":"2020","journal-title":"Ann Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib6","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ejca.2022.04.018","article-title":"European consensus-based interdisciplinary guideline for melanoma. Part 2: treatment - update 2022","volume":"170","author":"Garbe","year":"2022","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib7","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ejca.2020.02.021","article-title":"Survival of patients with advanced metastatic melanoma: the impact of MAP kinase pathway inhibition and immune checkpoint inhibition - update 2019","volume":"130","author":"Ugurel","year":"2020","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2021.100050","article-title":"A matching-adjusted indirect comparison of combination nivolumab plus ipilimumab with BRAF plus MEK inhibitors for the treatment of BRAF-mutant advanced melanoma","volume":"6","author":"Tarhini","year":"2021","journal-title":"ESMO Open"},{"key":"10.1016\/j.esmoop.2025.105053_bib9","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/s41416-020-01229-1","article-title":"First-line BRAF\/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis","volume":"124","author":"van Breeschoten","year":"2021","journal-title":"Br J Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1200\/JCO.22.01763","article-title":"Combination dabrafenib and trametinib versus combination nivolumab and ipilimumab for patients with advanced BRAF-mutant melanoma: the DREAMseq trial-ECOG-ACRIN EA6134","volume":"41","author":"Atkins","year":"2023","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib11","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1200\/JCO.21.02961","article-title":"Sequencing of ipilimumab plus nivolumab and encorafenib plus binimetinib for untreated BRAF-mutated metastatic melanoma (SECOMBIT): a randomized, three-arm, open-label phase II trial","volume":"41","author":"Ascierto","year":"2023","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib12","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41467-023-44475-6","article-title":"Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial","volume":"15","author":"Ascierto","year":"2024","journal-title":"Nat Commun"},{"key":"10.1016\/j.esmoop.2025.105053_bib13","doi-asserted-by":"crossref","DOI":"10.1056\/EVIDoa2400087","article-title":"Sequencing of checkpoint or BRAF\/MEK inhibitors on brain metastases in melanoma","volume":"3","author":"Ascierto","year":"2024","journal-title":"NEJM Evid"},{"key":"10.1016\/j.esmoop.2025.105053_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2023.112941","article-title":"Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: the ImmunoCobiVem phase 2 randomised trial","volume":"190","author":"Livingstone","year":"2023","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib15","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib16","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/S1470-2045(14)70301-8","article-title":"Combination of vemurafenib and cobimetinib in patients with advanced BRAF(V600)-mutated melanoma: a phase 1b study","volume":"15","author":"Ribas","year":"2014","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib17","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/S1470-2045(16)30122-X","article-title":"Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial","volume":"17","author":"Ascierto","year":"2016","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib18","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2024.42.17_suppl.LBA9503","article-title":"Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced BRAF-V600E\/K-mutated melanoma: the primary analysis of an EORTC randomized phase II study (EBIN)","volume":"42","author":"Robert","year":"2024","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa2407417","article-title":"Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma","volume":"392","author":"Wolchok","year":"2025","journal-title":"N Engl J Med"},{"key":"10.1016\/j.esmoop.2025.105053_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2024.114073","article-title":"COLUMBUS 7-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600E\/K-mutant melanoma","volume":"204","author":"Schadendorf","year":"2024","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib21","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s43018-021-00221-9","article-title":"Acquired resistance to anti-MAPK targeted therapy confers an immune-evasive tumor microenvironment and cross-resistance to immunotherapy in melanoma","volume":"2","author":"Haas","year":"2021","journal-title":"Nat Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib22","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.ccell.2021.07.023","article-title":"Anti-PD-1\/L1 lead-in before MAPK inhibitor combination maximizes antitumor immunity and efficacy","volume":"39","author":"Wang","year":"2021","journal-title":"Cancer Cell"},{"key":"10.1016\/j.esmoop.2025.105053_bib23","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1158\/1078-0432.CCR-11-2479","article-title":"Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma","volume":"18","author":"Wilmott","year":"2012","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.esmoop.2025.105053_bib24","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1158\/1078-0432.CCR-12-1630","article-title":"BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma","volume":"19","author":"Frederick","year":"2013","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.esmoop.2025.105053_bib25","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1158\/0008-5472.CAN-10-0118","article-title":"Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function","volume":"70","author":"Boni","year":"2010","journal-title":"Cancer Res"},{"key":"10.1016\/j.esmoop.2025.105053_bib26","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1158\/2326-6066.CIR-13-0160","article-title":"Paradoxical activation of T cells via augmented ERK signaling mediated by a RAF inhibitor","volume":"2","author":"Callahan","year":"2014","journal-title":"Cancer Immunol Res"},{"key":"10.1016\/j.esmoop.2025.105053_bib27","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-008606","article-title":"Tumor-targeted therapy with BRAF-inhibitor recruits activated dendritic cells to promote tumor immunity in melanoma","volume":"12","author":"Hornsteiner","year":"2024","journal-title":"J Immunother Cancer"},{"key":"10.1016\/j.esmoop.2025.105053_bib28","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1093\/annonc\/mdy116","article-title":"When is crossover desirable in cancer drug trials and when is it problematic?","volume":"29","author":"Haslam","year":"2018","journal-title":"Ann Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1200\/JCO.22.01354","article-title":"Melanoma: does sequencing really matter?","volume":"41","author":"Chandra","year":"2023","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.esmoop.2025.105053_bib30","doi-asserted-by":"crossref","first-page":"e461","DOI":"10.1016\/S1470-2045(23)00334-0","article-title":"Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study","volume":"24","author":"Dummer","year":"2023","journal-title":"Lancet Oncol"}],"container-title":["ESMO Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925009226?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702925009226?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:47:12Z","timestamp":1757576832000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2059702925009226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["S2059702925009226"],"URL":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.105053","relation":{},"ISSN":["2059-7029"],"issn-type":[{"value":"2059-7029","type":"print"}],"subject":[],"published":{"date-parts":[[2025,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Early switch from run-in with targeted to immunotherapy in advanced BRAFV600-positive melanoma: final results of the randomised phase II ImmunoCobiVem trial","name":"articletitle","label":"Article Title"},{"value":"ESMO Open","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.esmoop.2025.105053","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology.","name":"copyright","label":"Copyright"}],"article-number":"105053"}}