{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:35:10Z","timestamp":1774373710739,"version":"3.50.1"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>Using a customized, harmonized US electronic health record database, real-world prescription patterns of first-line adjuvant immunotherapy and targeted therapy were retrospectively assessed for <jats:italic toggle=\"yes\">BRAF<\/jats:italic>V600-mutated melanoma. Adults with <jats:italic toggle=\"yes\">BRAF<\/jats:italic>V600 mutation-positive stage IIIA-D cutaneous melanoma who received first-line adjuvant immunotherapy (nivolumab or pembrolizumab) or targeted therapy (dabrafenib plus trametinib) between 1 January 2014 and 30 August 2020 in the NOBLE database were included. Patients were followed from first-line adjuvant therapy initiation for at least 6\u2005months, until death, progression, follow-up loss, or data cutoff. Primary endpoints were proportion of patients receiving either therapy in first-line and second-line, treatment switching, treatment timing, and status at the end of first-line therapy. Secondary endpoints included discontinuation rates, recurrence-free survival (RFS), and overall survival (OS). Of 318 patients evaluated, 67.6% received nivolumab, 14.2% pembrolizumab, and 18.2% targeted therapy as first-line adjuvant therapy. Median treatment duration was longest for nivolumab (292\u2005days) and shortest for targeted therapy (115\u2005days). Reason for discontinuation was recorded for 195 of 274 patients who discontinued first-line therapy; most common reasons were treatment completion and treatment-related toxicity [87\/158 (55.0%) and 29\/158 (18.4%), respectively, in immunotherapy-treated patients; 9\/37 (24.3%) and 21\/37 (56.8%) in targeted therapy-treated patients]. Median RFS and OS for targeted therapy and nivolumab were not reached and were 34.6 and 38.1\u2005months, respectively, for pembrolizumab. These results inform on prescription preferences and clinical outcomes for <jats:italic toggle=\"yes\">BRAF<\/jats:italic>V600-mutated melanoma patients in the first-line adjuvant setting.<\/jats:p>","DOI":"10.1097\/cmr.0000000000000990","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T16:20:11Z","timestamp":1721146811000},"page":"457-464","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Real-world use and outcomes of targeted therapy and immunotherapy for adjuvant treatment of BRAF-mutated melanoma patients in the United States"],"prefix":"10.1097","volume":"34","author":[{"given":"Sanjay","family":"Chandrasekaran","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Li","family":"Ling","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackson","family":"Tang","sequence":"additional","affiliation":[{"name":"Asclepius Analytics, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"R1-20250528","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020.","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"R2-20250528","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1002\/cncr.31345","article-title":"Melanoma: what do all the mutations mean?","volume":"124","author":"Davis","year":"2018","journal-title":"Cancer"},{"key":"R3-20250528","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/CMR.0000000000000628","article-title":"Frequency of mutations in BRAF, NRAS, and KIT in different populations and histological subtypes of melanoma: a systemic review.","volume":"30","author":"Gutierrez-Castaneda","year":"2020","journal-title":"Melanoma Res"},{"key":"R4-20250528","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1200\/JCO.2010.32.4327","article-title":"Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma.","volume":"29","author":"Long","year":"2011","journal-title":"J Clin Oncol"},{"key":"R5-20250528","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.cell.2015.05.044","article-title":"Genomic classification of cutaneous melanoma.","volume":"161","year":"2015","journal-title":"Cell"},{"key":"R6-20250528","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer.","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"R7-20250528","doi-asserted-by":"crossref","first-page":"108200","DOI":"10.1016\/j.pharmthera.2022.108200","article-title":"The future of targeted kinase inhibitors in melanoma.","volume":"239","author":"Caksa","year":"2022","journal-title":"Pharmacol Ther"},{"key":"R8-20250528","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/jso.25298","article-title":"Updates in adjuvant systemic therapy for melanoma.","volume":"119","author":"Kwak","year":"2019","journal-title":"J Surg Oncol"},{"key":"R10-20250528","doi-asserted-by":"crossref","first-page":"738","DOI":"10.3390\/cancers12030738","article-title":"Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence.","volume":"12","author":"Vaddepally","year":"2020","journal-title":"Cancers (Basel)"},{"key":"R11-20250528","doi-asserted-by":"crossref","first-page":"367","DOI":"10.6004\/jnccn.2019.0018","article-title":"Cutaneous melanoma, version 2.2019, NCCN Clinical Practice Guidelines in Oncology.","volume":"17","author":"Coit","year":"2019","journal-title":"J Natl Compr Canc Netw"},{"key":"R16-20250528","doi-asserted-by":"crossref","first-page":"3947","DOI":"10.1200\/JCO.20.00198","article-title":"Systemic therapy for melanoma: ASCO guideline.","volume":"38","author":"Seth","year":"2020","journal-title":"J Clin Oncol"},{"key":"R17-20250528","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1056\/NEJMoa1802357","article-title":"Adjuvant pembrolizumab versus placebo in resected stage III melanoma.","volume":"378","author":"Eggermont","year":"2018","journal-title":"N Engl J Med"},{"key":"R18-20250528","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMoa1708539","article-title":"Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma.","volume":"377","author":"Long","year":"2017","journal-title":"N Engl J Med"},{"key":"R19-20250528","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa1709030","article-title":"Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma.","volume":"377","author":"Weber","year":"2017","journal-title":"N Engl J Med"},{"key":"R20-20250528","first-page":"422","article-title":"Prescription patterns, recurrence, and toxicity rates of adjuvant treatment for stage III\/IV melanoma-a real world single-center analysis.","volume":"11","author":"Hoffmann","year":"2022","journal-title":"Biology (Basel)"},{"key":"R21-20250528","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.3390\/cancers13102319","article-title":"Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients.","volume":"13","author":"Lodde","year":"2021","journal-title":"Cancers (Basel)"},{"key":"R24-20250528","doi-asserted-by":"crossref","first-page":"565","DOI":"10.5999\/aps.2012.39.5.565","article-title":"Management of malignant melanoma.","volume":"39","author":"Mun","year":"2012","journal-title":"Arch Plast Surg"},{"key":"R25-20250528","doi-asserted-by":"crossref","first-page":"S1316","DOI":"10.1016\/j.annonc.2021.08.2118","article-title":"SECOMBIT: The best sequential approach with combo immunotherapy [ipilimumab (I)\/nivolumab (N)] and combo target therapy [encorafenib (E)\/binimetinib (B)] in patients with BRAF mutated metastatic melanoma: a phase II randomized study.","volume":"32","author":"Ascierto","year":"2021","journal-title":"Ann Oncol"},{"key":"R26-20250528","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":"2022","journal-title":"J Clin Oncol"},{"key":"R27-20250528","doi-asserted-by":"crossref","first-page":"e000491","DOI":"10.1136\/esmoopen-2019-000491","article-title":"Tolerability of BRAF\/MEK inhibitor combinations: adverse event evaluation and management.","volume":"4","author":"Heinzerling","year":"2019","journal-title":"ESMO Open"},{"key":"R28-20250528","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1056\/NEJMoa1406037","article-title":"Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma.","volume":"371","author":"Long","year":"2014","journal-title":"N Engl J Med"},{"key":"R29-20250528","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-22-0689","article-title":"Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline.","volume":"187","author":"Husebye","year":"2022","journal-title":"Eur J Endocrinol"},{"key":"R30-20250528","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update.","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"R33-20250528","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S1470-2045(18)30261-4","article-title":"Cancer immunotherapy efficacy and patients\u2019 sex: a systematic review and meta-analysis.","volume":"19","author":"Conforti","year":"2018","journal-title":"Lancet Oncol"},{"key":"R34-20250528","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1158\/1078-0432.CCR-19-0137","article-title":"Sex hormones and anticancer immunity.","volume":"25","author":"Ozdemir","year":"2019","journal-title":"Clin Cancer Res"},{"key":"R35-20250528","doi-asserted-by":"crossref","first-page":"253","DOI":"10.5306\/wjco.v7.i2.253","article-title":"Off-label use of targeted therapies in oncology.","volume":"7","author":"Leveque","year":"2016","journal-title":"World J Clin Oncol"}],"container-title":["Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/CMR.0000000000000990","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T21:46:32Z","timestamp":1748468792000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/CMR.0000000000000990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024]]}},"URL":"https:\/\/doi.org\/10.1097\/cmr.0000000000000990","relation":{},"ISSN":["0960-8931","1473-5636"],"issn-type":[{"value":"0960-8931","type":"print"},{"value":"1473-5636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,16]]}}}