{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:23:17Z","timestamp":1772119397962,"version":"3.50.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"14","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Patients with\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>V600E<\/jats:italic>\n                      <\/jats:sup>\n                      -mutant metastatic colorectal cancer (mCRC) have a dismal prognosis. The best strategies in these patients remain elusive. Against this background, we report the clinical course of patients with\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>V600E<\/jats:italic>\n                      <\/jats:sup>\n                      -mutant mCRC to retrieve the best treatment strategy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>Clinico-pathological data were extracted from the electronic health records. Kaplan\u2013Meier method was used to estimate overall (OS) and progression-free survival (PFS). Objective response rate (ORR) was assessed according to RECIST 1.1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 51 patients were enrolled. FOLFOXIRI was administered to 12 patients; 29 patients received FOLFOX or FOLFIRI as first-line treatment. Median OS was 17.6\u00a0months. Median PFS with FOLFOXIRI (13.0\u00a0months) was significantly prolonged (HR 0.325) as compared to FOLFOX\/FOLFIRI (4.3\u00a0months). However, this failed to translate into an OS benefit (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.433). Interestingly, addition of a monoclonal antibody to chemotherapy associated with superior OS (HR 0.523). A total of 64.7% patients received further-line therapy, which included a BRAF inhibitor in 17 patients. Targeted therapy associated with very favourable OS (25.1\u00a0months).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Patients with BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                      -mutated mCRC benefit from the addition of an antibody to first-line chemotherapy. Further-line treatment including a BRAF inhibitor has a dramatic impact on survival.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-023-05141-y","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T03:05:49Z","timestamp":1689735949000},"page":"12903-12912","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of encorafenib on survival of patients with BRAFV600E-mutant metastatic colorectal cancer in a real-world setting"],"prefix":"10.1007","volume":"149","author":[{"given":"M.","family":"Zurloh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Goetz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Herold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Treckmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Markus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Albers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Rink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Rosery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Zaun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Kostbade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Pogorzelski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Ting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Stiens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Wiesweg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Schuler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kasper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Virchow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"issue":"8","key":"5141_CR1","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1093\/annonc\/mdx175","volume":"28","author":"D Arnold","year":"2017","unstructured":"Arnold D et al (2017) Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol 28(8):1713\u20131729","journal-title":"Ann Oncol"},{"issue":"3","key":"5141_CR2","doi-asserted-by":"publisher","first-page":"329","DOI":"10.6004\/jnccn.2021.0012","volume":"19","author":"AB Benson","year":"2021","unstructured":"Benson AB et al (2021) Colon cancer, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 19(3):329\u2013359","journal-title":"J Natl Compr Canc Netw"},{"issue":"6","key":"5141_CR3","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394\u2013424","journal-title":"CA Cancer J Clin"},{"issue":"12","key":"5141_CR4","doi-asserted-by":"publisher","first-page":"e711","DOI":"10.1111\/codi.12427","volume":"15","author":"C Clancy","year":"2013","unstructured":"Clancy C et al (2013) BRAF mutation is associated with distinct clinicopathological characteristics in colorectal cancer: a systematic review and meta-analysis. Colorectal Dis 15(12):e711-718","journal-title":"Colorectal Dis"},{"issue":"13","key":"5141_CR5","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/S1470-2045(15)00122-9","volume":"16","author":"C Cremolini","year":"2015","unstructured":"Cremolini C et al (2015) FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol 16(13):1306\u20131315","journal-title":"Lancet Oncol"},{"key":"5141_CR6","doi-asserted-by":"crossref","unstructured":"Cremolini C et al (2020) Individual patient data meta-analysis of FOLFOXIRI plus bevacizumab versus doublets plus bevacizumab as initial therapy of unresectable metastatic colorectal cancer. J Clin Oncol JCO2001225(28):3314\u20133324.","DOI":"10.1200\/JCO.20.01225"},{"issue":"4","key":"5141_CR7","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1093\/carcin\/bgh049","volume":"25","author":"K Fransen","year":"2004","unstructured":"Fransen K et al (2004) Mutation analysis of the BRAF, ARAF and RAF-1 genes in human colorectal adenocarcinomas. Carcinogenesis 25(4):527\u2013533","journal-title":"Carcinogenesis"},{"issue":"23","key":"5141_CR8","doi-asserted-by":"publisher","first-page":"2624","DOI":"10.1200\/JCO.2016.71.4394","volume":"35","author":"JC Jones","year":"2017","unstructured":"Jones JC et al (2017) (Non-V600) BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer. J Clin Oncol 35(23):2624\u20132630","journal-title":"J Clin Oncol"},{"issue":"17","key":"5141_CR9","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1056\/NEJMoa1908075","volume":"381","author":"S Kopetz","year":"2019","unstructured":"Kopetz S et al (2019) Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med 381(17):1632\u20131643","journal-title":"N Engl J Med"},{"issue":"1","key":"5141_CR10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/bjc.2015.399","volume":"114","author":"F Loupakis","year":"2016","unstructured":"Loupakis F et al (2016) Clinico-pathological nomogram for predicting BRAF mutational status of metastatic colorectal cancer. Br J Cancer 114(1):30\u201336","journal-title":"Br J Cancer"},{"issue":"9","key":"5141_CR11","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1093\/annonc\/mdw261","volume":"27","author":"DP Modest","year":"2016","unstructured":"Modest DP et al (2016) Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. Ann Oncol 27(9):1746\u20131753","journal-title":"Ann Oncol"},{"issue":"5","key":"5141_CR12","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.ejca.2015.01.054","volume":"51","author":"F Pietrantonio","year":"2015","unstructured":"Pietrantonio F et al (2015) Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer 51(5):587\u2013594","journal-title":"Eur J Cancer"},{"issue":"3","key":"5141_CR13","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1200\/JCO.2009.23.3452","volume":"28","author":"AD Roth","year":"2010","unstructured":"Roth AD et al (2010) Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 28(3):466\u2013474","journal-title":"J Clin Oncol"},{"issue":"12","key":"5141_CR14","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1038\/bjc.2015.173","volume":"112","author":"A Rowland","year":"2015","unstructured":"Rowland A et al (2015) Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. Br J Cancer 112(12):1888\u20131894","journal-title":"Br J Cancer"},{"issue":"1","key":"5141_CR15","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1053\/j.gastro.2014.09.041","volume":"148","author":"FA Sinicrope","year":"2015","unstructured":"Sinicrope FA et al (2015) Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology 148(1):88\u201399","journal-title":"Gastroenterology"},{"issue":"3","key":"5141_CR16","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/sj.bjc.6605164","volume":"101","author":"J Souglakos","year":"2009","unstructured":"Souglakos J et al (2009) Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 101(3):465\u2013472","journal-title":"Br J Cancer"},{"key":"5141_CR17","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ejca.2017.03.023","volume":"79","author":"S Stintzing","year":"2017","unstructured":"Stintzing S et al (2017) Impact of BRAF and RAS mutations on first-line efficacy of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab: analysis of the FIRE-3 (AIO KRK-0306) study. Eur J Cancer 79:50\u201360","journal-title":"Eur J Cancer"},{"issue":"15_suppl","key":"5141_CR18","doi-asserted-by":"publisher","first-page":"3502","DOI":"10.1200\/JCO.2021.39.15_suppl.3502","volume":"39","author":"S Stintzing","year":"2021","unstructured":"Stintzing S et al (2021) Randomized study to investigate FOLFOXIRI plus either bevacizumab or cetuximab as first-line treatment of BRAF V600E-mutant mCRC: the phase-II FIRE-4.5 study (AIO KRK-0116). J Clin Oncol 39(15_suppl):3502\u20133502","journal-title":"J Clin Oncol"},{"issue":"8","key":"5141_CR19","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1093\/annonc\/mdw235","volume":"27","author":"E Van Cutsem","year":"2016","unstructured":"Van Cutsem E et al (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27(8):1386\u20131422","journal-title":"Ann Oncol"},{"issue":"23","key":"5141_CR20","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1001\/jama.2017.7105","volume":"317","author":"AP Venook","year":"2017","unstructured":"Venook AP et al (2017) Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA 317(23):2392\u20132401","journal-title":"JAMA"},{"issue":"10","key":"5141_CR21","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.7150\/jca.30789","volume":"10","author":"J Wang","year":"2019","unstructured":"Wang J et al (2019) Clinicopathological significance of BRAF(V600E) mutation in colorectal cancer: an updated meta-analysis. J Cancer 10(10):2332\u20132341","journal-title":"J Cancer"},{"issue":"6","key":"5141_CR22","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1136\/gutjnl-2011-300865","volume":"61","author":"M Yamauchi","year":"2012","unstructured":"Yamauchi M et al (2012) Assessment of colorectal cancer molecular features along bowel subsites challenges the conception of distinct dichotomy of proximal versus distal colorectum. Gut 61(6):847\u2013854","journal-title":"Gut"},{"issue":"5","key":"5141_CR23","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/bjc.2011.19","volume":"104","author":"T Yokota","year":"2011","unstructured":"Yokota T et al (2011) BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer 104(5):856\u2013862","journal-title":"Br J Cancer"},{"issue":"1","key":"5141_CR24","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1093\/annonc\/mdy461","volume":"30","author":"T Yoshino","year":"2019","unstructured":"Yoshino T et al (2019) Biomarker analysis beyond angiogenesis: RAS\/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE-a global phase III study. Ann Oncol 30(1):124\u2013131","journal-title":"Ann Oncol"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-023-05141-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-023-05141-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-023-05141-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T04:08:48Z","timestamp":1697688528000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-023-05141-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":24,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["5141"],"URL":"https:\/\/doi.org\/10.1007\/s00432-023-05141-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3143154\/v1","asserted-by":"object"}]},"ISSN":["0171-5216","1432-1335"],"issn-type":[{"value":"0171-5216","type":"print"},{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,19]]},"assertion":[{"value":"5 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Martin Schuler received honoraria as consultant (compensated) from Amgen, AstraZeneca, BIOCAD, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda, Honoraries for CME presentations from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis and Research funding to institution from AstraZeneca, Bristol Myers-Squibb Stefan Kasper received honoraria from Merck Serono, MSD, Novartis, BMS, Amgen, Roche, Sanofi-Aventis, Servier, Incyte, Pierre Fabre and Lilly; research funding from Merck Serono, Lilly, BMS, Roche. Isabel Virchow received travel support from Pierre Fabre. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"MS received honoraria as consultant (compensated) from Amgen, AstraZeneca, BIOCAD, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda, Honoraries for CME presentations from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis and Research funding to institution from AstraZeneca, Bristol Myers-Squibb. SK received honoraria from Merck Serono, MSD, Novartis, BMS, Amgen, Roche, Sanofi-Aventis, Servier, Incyte, Pierre Fabre and Lilly; research funding from Merck Serono, Lilly, BMS, Roche. IV received travel support from Pierre Fabre. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}