{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T13:56:25Z","timestamp":1793368585698,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"ARCAD Foundation"},{"name":"Nuovo-Soldati Foundation"},{"DOI":"10.13039\/501100004097","name":"ARC Foundation for Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Servier Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>First-line therapeutic strategies for patients with BRAFV600E-mutated (BRAFmt) metastatic colorectal cancer (mCRC) mainly rely on subgroup analyses from randomized controlled trials (RCTs). We aimed to assess the prognostic and predictive impact of BRAFmt on the efficacy of targeted therapies with first-line chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Individual patient data from first-line RCTs with BRAF and KRAS status data in the ARCAD database were pooled. Progression-free survival and overall survival (OS) were assessed using Kaplan-Meier and Cox models. Outcomes were compared between treatment groups that were concurrently randomly assigned whenever possible.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 6391 patients from 10 RCTs were included: 573 BRAFmt (9.0%), 2059 KRASmt (32.2%), and 3759 double wild type (58.8%). BRAFmt mCRC patients experienced statistically significantly poorer OS than those with KRASmt (adjusted hazard ratio [HRadj] = 1.46, 95% confidence interval [CI] = 1.30 to 1.64) and patients with double wild-type tumors (HRadj = 2.14, 95% CI = 1.94 to 2.36). Anti-EGFR agents did not improve progression-free survival or OS of BRAFmt mCRC patients, based on 4 RCTs testing chemotherapy with or without anti-epidermal growth factor receptor (anti-EGFR) (HRadj = 0.96, 95% CI = 0.71 to 1.30; and HRadj = 0.85, 95% CI = 0.66 to 1.14, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that the addition of anti-EGFR agents to chemotherapy is ineffective as first-line treatment for BRAFmt mCRC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djab042","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T16:11:50Z","timestamp":1615824710000},"page":"1386-1395","source":"Crossref","is-referenced-by-count":48,"title":["<i>BRAF<\/i>\n                    V600E Mutation in First-Line Metastatic Colorectal Cancer: An Analysis of Individual Patient Data From the ARCAD Database"],"prefix":"10.1093","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-5162","authenticated-orcid":false,"given":"Romain","family":"Cohen","sequence":"first","affiliation":[{"name":"Department of Health Science Research, Mayo Clinic, Rochester, MN, USA"},{"name":"Department of Medical Oncology, Sorbonne University, Saint-Antoine Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heshan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Health Science Research, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Fiskum","sequence":"additional","affiliation":[{"name":"Department of Health Science Research, Mayo Clinic, Rochester, MN, 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University Hospitals Gasthuisberg Leuven and University of Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-6548","authenticated-orcid":false,"given":"Alan","family":"Venook","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Douillard","sequence":"additional","affiliation":[{"name":"University of Nantes Medical School Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1349-3321","authenticated-orcid":false,"given":"Volker","family":"Heinemann","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Comprehensive Cancer Center, University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis","family":"Ja Punt","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-2529","authenticated-orcid":false,"given":"Alfredo","family":"Falcone","sequence":"additional","affiliation":[{"name":"Department of Oncology, University of Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6071-7810","authenticated-orcid":false,"given":"Carsten","family":"Bokemeyer","sequence":"additional","affiliation":[{"name":"Department of Oncology, Haematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0189-8348","authenticated-orcid":false,"given":"Richard","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Medical Research Council Clinical Trials Unit, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-9568","authenticated-orcid":false,"given":"Heinz-Josef","family":"Lenz","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Keck School of Medicine at USC, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1550-1978","authenticated-orcid":false,"given":"Miriam","family":"Koopman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, the 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