2012
DOI: 10.1056/nejmoa1203421
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Abstract: Trametinib, as compared with chemotherapy, improved rates of progression-free and overall survival among patients who had metastatic melanoma with a BRAF V600E or V600K mutation. (Funded by GlaxoSmithKline; METRIC ClinicalTrials.gov number, NCT01245062.).

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Cited by 1,897 publications
(1,421 citation statements)
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“…The MAPK signaling pathway is a key regulator of cell growth and survival, and it is overactivated in nearly 30% of human cancers. 58 Two MEK inhibitors, trametinib and cobimetinib, 59,60 are currently approved for the treatment of melanoma and more than 10 other MEK1/2 inhibitors are in various stages of clinical testing across a spectrum of cancer types including breast cancer. 61 In addition to its cell-intrinsic protumorigenic effects, MAPK signaling has also been implicated in the upregulation of checkpoint ligands such as PD-L1.…”
Section: Discussionmentioning
confidence: 99%
“…The MAPK signaling pathway is a key regulator of cell growth and survival, and it is overactivated in nearly 30% of human cancers. 58 Two MEK inhibitors, trametinib and cobimetinib, 59,60 are currently approved for the treatment of melanoma and more than 10 other MEK1/2 inhibitors are in various stages of clinical testing across a spectrum of cancer types including breast cancer. 61 In addition to its cell-intrinsic protumorigenic effects, MAPK signaling has also been implicated in the upregulation of checkpoint ligands such as PD-L1.…”
Section: Discussionmentioning
confidence: 99%
“…Trametinib was the first MEK inhibitor to gain regulatory approval for use as a single agent. In the phase III METRIC trial 53 , this agent was associated with an ORR of 22% and a median PFS of 4.8 months (TABLE 2), with common toxicities that included skin manifestations, diarrhoea, and fatigue, and less-common cardiac and ocular toxicities (such as cardiomyopathy and retinopathies, respectively). In parallel with the clinical development of BRAF and MEK inhibitors, translational investigations were elucidating the mechanistic underpinnings of molecular signalling through the MAPK pathway, and mechanisms of resistance to BRAF-inhibitor monotherapy 54 .…”
Section: Braf-targeted Therapiesmentioning
confidence: 99%
“…MEK inhibitors, such as trametinib, cobimetinib and selumetinib exert their inhibitory effect by targeting a different kinase located downstream at the same pathway. Trametinib increased response and overall survival rates when compared to chemotherapy in melanoma patients harboring B-Raf mutations (Flaherty et al, 2012). As MEK inhibitors theoretically can be effective in patients harboring B-Raf non-V600 mutations, this may be an interesting therapeutic option for NSCLC patients harboring non-V600 BRAF mutations.…”
Section: Overcoming Resistancementioning
confidence: 99%