{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T02:33:07Z","timestamp":1781490787078,"version":"3.54.1"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Targeted therapy with a combination of dabrafenib and trametinib has been developed and widely used for treatment of melanoma. However, data regarding its safety and efficacy in Japanese patients with malignant melanoma are limited. A post\u2010marketing surveillance (PMS) study was conducted to investigate the safety and efficacy of combination therapy in a Japanese clinical setting with a surveillance period of June 2016 to March 2022; 326 patients with unresectable malignant melanoma with <jats:italic>BRAF<\/jats:italic> mutation were enrolled. The interim results were published in July 2020. Herein, we report the results of the final analysis based on the data collected until the completion of the PMS study. The safety analysis population included 326 patients, the majority of whom had stage IV disease (79.14%) and Eastern Cooperative Oncology Group performance status 0 or 1 (85.28%). All patients were treated with the approved dose of dabrafenib, while 99.08% were treated with the approved dose of trametinib. Adverse events (AEs) occurred in 282 patients (86.50%) and the major AEs (incidence \u22655%) were pyrexia (47.85%), malignant melanoma (33.44%), hepatic function abnormal (9.82%), rash and blood creatine phosphokinase increased (8.59% each), malaise (6.44%), nausea (5.52%), and diarrhea and rhabdomyolysis (5.21% each). The incidences rates of adverse drug reactions of safety specifications were 45.71% for pyrexia, 15.95% for hepatic impairment, 12.58% for rhabdomyolysis, 4.60% for cardiac disorders, and 3.07% for eye disorders. In the efficacy analysis population of 318 patients, the objective response rate was 58.18% (95% confidence interval [CI] 52.54%\u201363.66%). The progression\u2010free survival rates at 90, 180, and 360\u2009days were 88.14% (95% CI 84.00%\u201391.26%), 69.53% (63.85%\u201374.50%), and 52.07% (45.71%\u201358.03%), respectively. Consistent with previous interim results, no new safety or efficacy concerns were observed in this final analysis of a PMS study conducted in a Japanese real\u2010world clinical setting.<\/jats:p>","DOI":"10.1111\/1346-8138.16759","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T05:24:16Z","timestamp":1678339456000},"page":"727-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Final analysis of a post\u2010marketing surveillance study of dabrafenib and trametinib combination therapy in Japanese patients with unresectable malignant melanoma with <i>BRAF<\/i> V600 mutation"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-9319","authenticated-orcid":false,"given":"Tomoaki","family":"Kaizuka","sequence":"first","affiliation":[{"name":"Global Drug Development Division Novartis Pharma K.K.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryohei","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Global Drug Development Division Novartis Pharma K.K.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Harumiya","sequence":"additional","affiliation":[{"name":"Global Drug Development Division Novartis Pharma K.K.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Innovative Medicines International Japan Novartis Pharma K.K.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Ushida","sequence":"additional","affiliation":[{"name":"Global Drug Development Division Novartis Pharma K.K.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0190"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/OP.21.00686"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.670726"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-019-0607-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.05.009"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406037"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412690"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.14210"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15204"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.12.021"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-020-01737-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.12.015"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu529"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.07.016"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16759","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1346-8138.16759","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.16759","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T09:39:01Z","timestamp":1692524341000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.16759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":14,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1111\/1346-8138.16759"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.16759","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"value":"0385-2407","type":"print"},{"value":"1346-8138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]},"assertion":[{"value":"2022-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}