Ipilimumab, Vemurafenib, Dabrafenib, and Trametinib: Synergistic Competitors in the Clinical Management of BRAF Mutant Malignant Melanoma

被引:63
作者
Luke, Jason J. [1 ]
Hodi, F. Stephen
机构
[1] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA
关键词
CTLA-4; Immunotherapy; BRAF; MEK; Resistance; Biomarker; MEK INHIBITOR TRAMETINIB; UNRESECTABLE STAGE-III; METASTATIC MELANOMA; OPEN-LABEL; PHASE-II; COMBINATION IMMUNOTHERAPY; SELECTIVE INHIBITOR; ACQUIRED-RESISTANCE; ANTIGEN-4; ANTIBODY; IMPROVED SURVIVAL;
D O I
10.1634/theoncologist.2012-0391
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
There have been significant advances in the treatment of malignant melanoma with the U.S. Food and Drug Administration approval of two drugs in 2011, the first drugs approved in 13 years. The developments of immune checkpoint modulation via cytotoxic T-lymphocyte antigen-4 blockade, with ipilimumab, and targeting of BRAF(V600), with vemurafenib or dabrafenib, as well as MEK, with trametinib, have been paradigm changing both for melanoma clinical practice and for oncology therapeutic development. These advancements, however, reveal new clinical questions regarding combinations and optimal sequencing of these agents in patients with BRAF mutant disease. We review the development of these agents, putative biomarkers, and resistance mechanisms relevant to their use, and possibilities for sequencing and combining these agents.
引用
收藏
页码:717 / 725
页数:9
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