{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T09:38:09Z","timestamp":1768988289638,"version":"3.49.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma K.K.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Purpose<\/jats:title>\n<jats:p>To investigate the safety and efficacy of dabrafenib and trametinib combination therapy for <jats:italic>BRAF<\/jats:italic> V600 mutation-positive unresectable and metastatic melanoma in over 100 Japanese patients of a real-world clinical setting.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Patients<\/jats:title>\n<jats:p>The surveillance period of interim post-marketing surveillance (PMS) analysis was from June 2016 to November 2018, and 112 patients with unresectable and metastatic <jats:italic>BRAF<\/jats:italic> V600 melanoma who received dabrafenib and trametinib were enrolled.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The safety analysis set included 112 patients whom almost all patients had stage IV disease (<jats:italic>n<\/jats:italic>\u2009=\u200997, 86.61%) with an Eastern Cooperative Oncology Group performance status 0 or 1 (<jats:italic>n<\/jats:italic>\u2009=\u2009102, 91.07%), and mean (standard deviation) lactate dehydrogenase level was 354.3 (456.4) U\/L (<jats:italic>n<\/jats:italic>\u2009=\u2009105) at baseline. Median daily dose of dabrafenib was 300.0\u00a0mg\/day (118\u2013300), and median daily dose of trametinib was 2.00\u00a0mg\/day (1.0\u20134.0). Adverse drug reactions (ADRs) were reported in 84 patients (75%), and common ADRs (incidence\u2009\u2265\u20095%) were pyrexia (<jats:italic>n<\/jats:italic>\u2009=\u200949, 43.75%), hepatic function abnormal (<jats:italic>n<\/jats:italic>\u2009=\u200911, 9.82%), rash and blood creatine phosphokinase increased (<jats:italic>n<\/jats:italic>\u2009=\u20099 each, 8.04%), and erythema nodosum (<jats:italic>n<\/jats:italic>\u2009=\u20096, 5.36%). Majority of ADRs reported in this study were consistent with that reported in previous trials. In the efficacy analysis set of 110 patients, the objective response rate was 55.45% (95% confidence interval 45.67\u201364.93%), and median progression-free survival was 384.0\u00a0days (251.0\u00a0days-not reached).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>No new safety or efficacy concerns were observed in this interim PMS analysis in Japanese patients with unresectable and metastatic melanoma with <jats:italic>BRAF<\/jats:italic> gene mutation who received dabrafenib and trametinib combination therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s10147-020-01737-3","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T09:07:50Z","timestamp":1595408870000},"page":"1870-1878","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interim analysis for post-marketing surveillance of dabrafenib and trametinib combination therapy in Japanese patients with unresectable and metastatic melanoma with BRAF V600 mutation"],"prefix":"10.1007","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-6175","authenticated-orcid":false,"given":"Yasutomo","family":"Teshima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minako","family":"Kizaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryohei","family":"Kurihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Kano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Harumiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,22]]},"reference":[{"key":"1737_CR1","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1101\/gad.191999.112","volume":"26","author":"H Tsao","year":"2012","unstructured":"Tsao H, Chin L, Garraway LA et al (2012) Melanoma: from mutations to medicine. 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