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Currently, it is unclear how existing therapies can be best used to prevent or treat brain metastasis in melanoma patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>We aimed to assess brain metastasis free survival (BMFS), overall survival (OS), incidence of brain metastases, and sequencing strategies of immunotherapy and targeted therapy in patients with BRAF\u2010mutated advanced melanoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We retrospectively analyzed 683 patients with BRAF\u2010mutated advanced melanoma treated with first line (1L) immunotherapy (<jats:italic>N<\/jats:italic>\u00a0=\u2009266) or targeted therapy (<jats:italic>N<\/jats:italic>\u00a0=\u2009417). The primary outcome was BMFS. Secondary outcomes included OS of all patients and incidence of brain metastases in patients without documented brain metastases prior to 1L therapy. The median BMFS was 13.7 months [95% confidence interval (CI): 12.4\u201316.0] among all patients. The median BMFS for patients receiving 1L immunotherapy was 41.9 months [95% CI: 22.8\u2013not reached (NR)] and targeted therapy was 11.0 months (95% CI: 8.8\u201312.5). Median OS results were qualitatively similar to BMFS results. The cumulative incidence of brain metastases for patients receiving 1L targeted therapy was higher than for patients receiving 1L immunotherapy (<jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.001). Patients receiving 1L anti\u2010CTLA4 plus anti\u2010PD1 combination immunotherapy only or followed by second line (2L) targeted therapy had better BMFS (HR 0.40, 95% CI: 0.24\u20130.67,<jats:italic>P<\/jats:italic>\u00a0=\u2009.001), improved OS (HR 0.49, 95% CI: 0.30\u20130.81,<jats:italic>P<\/jats:italic>\u00a0=\u2009.005), and reduced incidence of brain metastases (HR 0.47, 95% CI: 0.24\u20130.67,<jats:italic>P<\/jats:italic>\u00a0=\u2009.047) than patients receiving 1L combination BRAF and MEK targeted therapy followed by 2L immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with advanced BRAF mutant melanoma treated with 1L immunotherapy have significantly longer BMFS and OS, and reduced incidence of brain metastases, compared with those treated with 1L targeted therapy. Further studies evaluating the ability of immunotherapy and targeted therapy to improve OS and prevent brain metastases are warranted<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.1419","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T08:47:35Z","timestamp":1623919655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["First line immunotherapy extends brain metastasis free survival, improves overall survival, and reduces the incidence of brain metastasis in patients with advanced melanoma"],"prefix":"10.1002","volume":"4","author":[{"given":"Xuechen","family":"Wang","sequence":"first","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Health Sciences Center Salt Lake City Utah USA"},{"name":"Department of Population Health Sciences University of Utah Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Haaland","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Health Sciences Center Salt Lake City Utah USA"},{"name":"Department of Population Health Sciences University of Utah Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwen","family":"Hu\u2010Lieskovan","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Health Sciences Center Salt Lake City Utah USA"},{"name":"Department of Internal Medicine University of Utah Health Sciences Center Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard","family":"Colman","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Health Sciences Center Salt Lake City Utah USA"},{"name":"Department of Neurosurgery University of Utah Health Sciences Center Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6411-6032","authenticated-orcid":false,"given":"Sheri L.","family":"Holmen","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah Health Sciences Center Salt Lake City Utah USA"},{"name":"Department of Surgery University of Utah Health Sciences Center Salt Lake City Utah USA"},{"name":"Department of Oncological Sciences University of Utah Health Sciences Center Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.51.1.15"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.12-7-864"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203421"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406037"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30142-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1302369"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.3377"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)70122-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709030"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802357"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708539"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2964(78)90201-3"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25634"},{"key":"e_1_2_10_18_1","first-page":"572","article-title":"Survival rates of patients with metastatic malignant melanoma","volume":"7","author":"Sandru A","year":"2014","journal-title":"J Med Life"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1998.88.1.0011"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30946"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03033729"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3053"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197808)42:2<660::AID-CNCR2820420237>3.0.CO;2-E"},{"volume-title":"Diagnosis and Treatment Options for Brain Metastasis of Melanoma","year":"2011","author":"Chaichana K. 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