{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:16:54Z","timestamp":1783603014829,"version":"3.55.0"},"reference-count":34,"publisher":"Harborside Press, LLC","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:p>\n                    The recent approval of encorafenib, cetuximab, and FOLFOX based on the phase III BREAKWATER trial has introduced a new standard of care for the first-line treatment of\n                    <jats:italic>BRAF<\/jats:italic>\n                    V600E\u2013mutated metastatic colorectal cancer (mCRC). However, its safety and efficacy in patients with significant liver dysfunction remains unclear and, as such, patients are often excluded from pivotal clinical trials. This report presents a case of\n                    <jats:italic>BRAF<\/jats:italic>\n                    V600E\u2013mutated mCRC presenting with extensive hepatic involvement and liver dysfunction. Despite the absence of guidelines, the patient was initiated on full-dose encorafenib, cetuximab, and FOLFOX. He experienced a rapid clinical and biochemical response, with near-normalization of liver enzymes after cycle 1, and complete functional recovery by cycle 3. Treatment was well tolerated, with no significant adverse events throughout 9 cycles. He subsequently transitioned to maintenance 5-FU, cetuximab, and encorafenib. Posttreatment blood-based next-generation sequencing revealed no residual actionable mutations. The patient then successfully underwent complete surgical resection of his primary tumor and metastatic disease with negative margins. This case highlights the importance of considering encorafenib-based therapy in select patients with\n                    <jats:italic>BRAF<\/jats:italic>\n                    V600E\u2013mutated mCRC in the setting of compromised liver function.\n                  <\/jats:p>","DOI":"10.6004\/jnccn.2026.7003","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:50:29Z","timestamp":1780577429000},"source":"Crossref","is-referenced-by-count":0,"title":["Successful Management of BRAF V600E\u2013Mutated Metastatic Colorectal Cancer With Liver Dysfunction Using Encorafenib-Based Therapy"],"prefix":"10.6004","volume":"24","author":[{"given":"Celine","family":"Hoyek","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Pirozzi","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ"},{"name":"Department of Biomedical Sciences, Humanitas University, Milan, Italy"},{"name":"Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley","family":"Rone","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanios","family":"Bekaii-Saab","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"Am Soc Clin Oncol Educ Book","first-page":"231","article-title":"Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer","volume":"38","author":"Dienstmann R","year":"2018","unstructured":"Dienstmann R, Salazar R, Tabernero J. Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer. Am Soc Clin Oncol Educ Book 2018;38:231\u2013238."},{"key":"B2","series-title":"Am Soc Clin Oncol Educ Book","first-page":"1","article-title":"The evolving treatment landscape in BRAF-V600E-mutated metastatic colorectal cancer","volume":"42","author":"Tabernero J","year":"2022","unstructured":"Tabernero J, Ros J, Elez E. The evolving treatment landscape in BRAF-V600E-mutated metastatic colorectal cancer. Am Soc Clin Oncol Educ Book 2022;42:1\u201310."},{"key":"B3","series-title":"Genes (Basel)","article-title":"Emerging BRAF mutations in cancer progression and their possible effects on transcriptional networks","volume":"11","year":"2020","unstructured":"\u015amiech M, Leszczy\u0144ski P, Kono H,  Emerging BRAF mutations in cancer progression and their possible effects on transcriptional networks. Genes (Basel) 2020;11:1342."},{"key":"B4","series-title":"Ann Oncol","first-page":"1746","article-title":"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","volume":"27","author":"Modest DP","year":"2016","unstructured":"Modest DP, Ricard I, Heinemann V,  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 2016;27:1746\u20131753."},{"key":"B5","series-title":"N Engl J Med","first-page":"1609","article-title":"Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer","volume":"371","author":"Loupakis F","year":"2014","unstructured":"Loupakis F, Cremolini C, Masi G,  Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 2014;371:1609\u20131618."},{"key":"B6","series-title":"J Clin Oncol","article-title":"Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406)","volume":"35(Suppl)","author":"Kopetz S","year":"2017","unstructured":"Kopetz S, McDonough SL, Morris VK,  Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406). J Clin Oncol 2017;35(Suppl):Abstract 520."},{"key":"B7","series-title":"J Clin Oncol","first-page":"273","article-title":"Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study","volume":"39","author":"Tabernero J","year":"2021","unstructured":"Tabernero J, Grothey A, Van Cutsem E,  Encorafenib plus cetuximab as a new standard of care for previously treated BRAF V600E-mutant metastatic colorectal cancer: updated survival results and subgroup analyses from the BEACON study. J Clin Oncol 2021;39:273\u2013284."},{"key":"B8","series-title":"N Engl J Med","first-page":"1632","article-title":"Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer","volume":"381","author":"Kopetz S","year":"2019","unstructured":"Kopetz S, Grothey A, Yaeger R,  Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Engl J Med 2019;381:1632\u20131643."},{"key":"B9","series-title":"Nat Med","first-page":"901","article-title":"Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial","volume":"31","author":"Kopetz S","year":"2025","unstructured":"Kopetz S, Yoshino T, Van Cutsem E,  Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial. Nat Med 2025;31:901\u2013908."},{"key":"B10","series-title":"Ann Surg","first-page":"494","article-title":"Time of metastasis and outcome in colorectal cancer","volume":"269","author":"Rahbari NN","year":"2019","unstructured":"Rahbari NN, Carr PR, Jansen L,  Time of metastasis and outcome in colorectal cancer. Ann Surg 2019;269:494\u2013502."},{"key":"B11","series-title":"Ann Oncol","first-page":"1386","article-title":"ESMO consensus guidelines for the management of patients with metastatic colorectal cancer","volume":"27","author":"Van Cutsem E","year":"2016","unstructured":"Van Cutsem E, Cervantes A, Adam R,  ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 2016;27:1386\u20131422."},{"key":"B12","series-title":"Ann Oncol","first-page":"2396","article-title":"The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients","volume":"21","author":"Fari\u00f1a-Sarasqueta A","year":"2010","unstructured":"Fari\u00f1a-Sarasqueta A, van Lijnschoten G, Moerland E,  The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients. Ann Oncol 2010;21:2396\u20132402."},{"key":"B13","series-title":"World J Surg Oncol","first-page":"241","article-title":"Associations between BRAF(V600E) and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis","volume":"14","author":"Liu C","year":"2016","unstructured":"Liu C, Chen T, Liu Z. Associations between BRAF(V600E) and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World J Surg Oncol 2016;14:241."},{"key":"B14","series-title":"Ann Oncol","first-page":"10","article-title":"Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up","volume":"34","author":"Cervantes A","year":"2023","unstructured":"Cervantes A, Adam R, Rosell\u00f3 S,  Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol 2023;34:10\u201332."},{"key":"B15","series-title":"Ann Oncol","first-page":"1142","article-title":"Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunction","volume":"14","author":"Fleming GF","year":"2003","unstructured":"Fleming GF, Schilsky RL, Schumm LP,  Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunction. Ann Oncol 2003;14:1142\u20131147."},{"key":"B16","series-title":"Gastrointest Cancer Res","first-page":"171","article-title":"Cetuximab for patients with colon cancer and hepatic metastasis complicated by liver dysfunction and icterus","volume":"3","author":"Shitara K","year":"2009","unstructured":"Shitara K, Yokota T, Utsunomiya S. Cetuximab for patients with colon cancer and hepatic metastasis complicated by liver dysfunction and icterus. Gastrointest Cancer Res 2009;3:171\u2013172."},{"key":"B17","series-title":"Cancer Chemother Pharmacol","first-page":"1303","article-title":"Pharmacokinetics and safety of cetuximab in a patient with renal dysfunction","volume":"73","author":"Krens LL","year":"2014","unstructured":"Krens LL, Baas JM, Verboom MC,  Pharmacokinetics and safety of cetuximab in a patient with renal dysfunction. Cancer Chemother Pharmacol 2014;73:1303\u20131306."},{"key":"B18","series-title":"Semin Oncol","first-page":"82","article-title":"Clinical pharmacokinetics of fluorouracil and folinic acid","volume":"19(Suppl)","author":"Schalhorn A","year":"1992","unstructured":"Schalhorn A, K\u00fchl M. Clinical pharmacokinetics of fluorouracil and folinic acid. Semin Oncol 1992;19(Suppl):82\u201392."},{"key":"B19","series-title":"Oncology (Williston Park)","first-page":"13","article-title":"Biochemical and clinical pharmacology of 5-fluorouracil","volume":"12(Suppl)","author":"Schilsky RL","year":"1998","unstructured":"Schilsky RL. Biochemical and clinical pharmacology of 5-fluorouracil. Oncology (Williston Park) 1998;12(Suppl):13\u201318."},{"key":"B20","series-title":"Clin Cancer Res","first-page":"1205","article-title":"Clinical pharmacokinetics of oxaliplatin: a critical review","volume":"6","author":"Graham MA","year":"2000","unstructured":"Graham MA, Lockwood GF, Greenslade D,  Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res 2000;6:1205\u20131218."},{"key":"B21","series-title":"J Pharm Sci","first-page":"3879","article-title":"New insights into the biotransformation and pharmacokinetics of oxaliplatin","volume":"98","author":"Jerremalm E","year":"2009","unstructured":"Jerremalm E, Wallin I, Ehrsson H. New insights into the biotransformation and pharmacokinetics of oxaliplatin. J Pharm Sci 2009;98:3879\u20133885."},{"key":"B22","series-title":"Semin Oncol","first-page":"14","article-title":"Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction: a preliminary report of the National Cancer Institute Organ Dysfunction Working Group","volume":"30(Suppl)","author":"Doroshow JH","year":"2003","unstructured":"Doroshow JH, Synold TW, Gandara D,  Pharmacology of oxaliplatin in solid tumor patients with hepatic dysfunction: a preliminary report of the National Cancer Institute Organ Dysfunction Working Group. Semin Oncol 2003;30(Suppl):14\u201319."},{"key":"B23","series-title":"Clin Colorectal Cancer","first-page":"E6","article-title":"Safe use of FOLFOX in two patients with metastatic colorectal carcinoma and severe hepatic dysfunction","volume":"10","author":"Roderburg C","year":"2011","unstructured":"Roderburg C, do O N, Fuchs R,  Safe use of FOLFOX in two patients with metastatic colorectal carcinoma and severe hepatic dysfunction. Clin Colorectal Cancer 2011;10:E6\u20139."},{"key":"B24","series-title":"Gan To Kagaku Ryoho","first-page":"1115","article-title":"A case of metastatic colorectal cancer with icterus due to multiple liver metastases treated effectively by FOLFOX plus bevacizumab [in Japanese]","volume":"40","author":"Terasawa T","year":"2013","unstructured":"Terasawa T, Koja S, Yasuda K, Fukuda K. A case of metastatic colorectal cancer with icterus due to multiple liver metastases treated effectively by FOLFOX plus bevacizumab [in Japanese]. Gan To Kagaku Ryoho 2013;40:1115\u20131118."},{"key":"B25","series-title":"J Gastrointest Cancer","first-page":"68","article-title":"Metastatic colorectal cancer with severe liver dysfunction successfully treated using FOLFOX therapy","volume":"42","author":"Shimura T","year":"2011","unstructured":"Shimura T, Kataoka H, Hirata Y,  Metastatic colorectal cancer with severe liver dysfunction successfully treated using FOLFOX therapy. J Gastrointest Cancer 2011;42:68\u201372."},{"key":"B26","series-title":"J Natl Compr Canc Netw","first-page":"155","article-title":"Safety and efficacy of FOLFOX followed by cetuximab for metastatic colorectal cancer with severe liver dysfunction","volume":"12","author":"Elsoueidi R","year":"2014","unstructured":"Elsoueidi R, Craig J, Mourad H,  Safety and efficacy of FOLFOX followed by cetuximab for metastatic colorectal cancer with severe liver dysfunction. J Natl Compr Canc Netw 2014;12:155\u2013160."},{"key":"B27","series-title":"Oncology","first-page":"222","article-title":"5-fluorouracil leucovorin and oxaliplatin (FOLFOX) in the treatment of metastatic colon cancer with severe liver dysfunction","volume":"67","author":"Fakih MG","year":"2004","unstructured":"Fakih MG. 5-fluorouracil leucovorin and oxaliplatin (FOLFOX) in the treatment of metastatic colon cancer with severe liver dysfunction. Oncology 2004;67:222\u2013224."},{"key":"B28","series-title":"Mol Pharmacol","first-page":"608","article-title":"Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38)","volume":"62","author":"Gagn\u00e9 JF","year":"2002","unstructured":"Gagn\u00e9 JF, Montminy V, Belanger P,  Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Mol Pharmacol 2002;62:608\u2013617."},{"key":"B29","series-title":"Cancer Chemother Pharmacol","first-page":"176","article-title":"Identification and kinetics of a beta-glucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan","volume":"36","author":"Rivory LP","year":"1995","unstructured":"Rivory LP, Robert J. Identification and kinetics of a beta-glucuronide metabolite of SN-38 in human plasma after administration of the camptothecin derivative irinotecan. Cancer Chemother Pharmacol 1995;36:176\u2013179."},{"key":"B30","article-title":"Braftovi, INN-encorafenib","unstructured":"European Medicines Agency. Braftovi, INN-encorafenib. Accessed January 20, 2026. Available at: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/braftovi-epar-product-information_en.pdf"},{"key":"B31","article-title":"BRAFTOVI (encorafenib) capsules","year":"2024","unstructured":"BRAFTOVI (encorafenib) capsules. Prescribing information. Array BioPharma Inc.; 2024. Accessed January 20, 2026. Available at: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/210496s018lbl.pdf"},{"key":"B32","series-title":"Front Oncol","first-page":"1102330","article-title":"Safety and rapid response of dabrafenib and trametinib therapy during hyperbilirubinemia in metastatic melanoma","volume":"13","author":"Shalata W","year":"2023","unstructured":"Shalata W, Steckbeck R, Polishchuk I,  Safety and rapid response of dabrafenib and trametinib therapy during hyperbilirubinemia in metastatic melanoma. Front Oncol 2023;13:1102330."},{"key":"B33","series-title":"BMC Cancer","first-page":"731","article-title":"The survival impact of palliative chemotherapy dose modifications on metastatic colon cancer","volume":"22","author":"Zainal Abidin MN","year":"2022","unstructured":"Zainal Abidin MN, Omar MS, Islahudin F,  The survival impact of palliative chemotherapy dose modifications on metastatic colon cancer. BMC Cancer 2022;22:731."},{"key":"B34","article-title":"Safety announcement: FDA highlights importance of DPD deficiency discussions with patients prior to capecitabine or 5FU treatment","unstructured":"Food and Drug Administration. Safety announcement: FDA highlights importance of DPD deficiency discussions with patients prior to capecitabine or 5FU treatment. Accessed January 24, 2025. Available from: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/safety-announcement-fda-highlights-importance-dpd-deficiency-discussions-patients-prior-capecitabine"}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/7\/article-e267003.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/7\/article-e267003.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/7\/article-e267003.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:41:40Z","timestamp":1783600900000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/7\/article-e267003.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":34,"journal-issue":{"issue":"7"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2026.7003","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]}}}