MEK Inhibitor Active in NRAS-Mutated Melanoma

The MEK inhibitor MEK162 is the first agent to show some activity in patients with NRAS– and BRAF-mutated advanced melanoma, according to the conclusions of a phase II study, evaluating the drug’s safety and efficacy, published in Lancet Oncology. In addition, treatment with MEK162 resulted in the shrinkage of target brain metastases in two patients.


Research paper here: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70024-X/abstract


New Phase III study will test BRAF/MEK combination therapy in melanoma patients with BRAF positive mutation after following surgery

The London-based company, GSK has stared a phase III trial called “COMBI-AD” that will test the combination of a BRAF and MEK inhibitor, dabrafenib and trametinib in patients with BRAF V600E mutation-positive melanoma who have had surgery to remove their tumors (adjuvant setting). The placebo-controlled trial is testing how long the combo treatment can delay or prevent cancer recurrence in these high-risk patients. Two phase III combination trials are currently ongoing to test the combination versus monotherapy in metastatic BRAF-positive melanoma patients. 


Europe Accelerates Trametinib Review

The European Medicines Agency has granted a speedy review of trametinib, an experimental MEK inhibitor made by pharmaceutical company GlaxoSmithKline. The firm’s application for a European license includes findings from two studies of melanomas that have BRAF V600 mutations: a phase III trial comparing trametinib to two standard chemotherapy drugs (dacarbazine and paclitaxel) and a phase I/II trial comparing trametinib alone and in combination with the experimental BRAF-inhibitor dabrafenib. If approved, trametinib could be available to people with melanoma within 6 months.


Plexxikon updates Zelboraf Phase 1 data on BRAF V600E mutation-positive melanoma

Plexxikon today announced that updated Phase 1 clinical data of Zelboraf (vemurafenib) were presented at the Society for Melanoma Research (SMR) 2012 Congress, held November 8-11 in Los Angeles, CA.


Combined BRAF and MEK Inhibition Improves Outcome in Metastatic Melanoma

The combination of dabrafenib and trametinib is safe and effective in BRAF-mutant melanoma.


Watchdog approves skin cancer drugs ipilimumab and vemurafenib

Patients with an advanced form of skin cancer were given new hope today after the health watchdog recommended that two life-extending treatments should be available on the NHS.


PLOS ONE: The Prognostic Value of BRAF Mutation in Colorectal Cancer and Melanoma: A Systematic Review and Meta-Analysis

PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.


Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

Vemurafenib, a selective RAF inhibitor, extends survival among patients with BRAF V600E–mutant melanoma. Vemurafenib inhibits ERK signaling in BRAF V600E–mutant cells but activates ERK signaling in BRAF wild-type cells. This paradoxical activation of ERK signaling is the mechanistic basis for the development of RAS-mutant squamous-cell skin cancers in patients treated with RAF inhibitors. This study reports the accelerated growth of a previously unsuspected RAS-mutant leukemia in a patient with melanoma who was receiving vemurafenib. Exposure to vemurafenib induced hyperactivation of ERK signaling and proliferation of the leukemic cell population, an effect that was reversed on drug withdrawal.


New melanoma trial initiated at Moffitt Cancer Center to investigate utility of immunotherapy biomarkers

Phase I melanoma patient trial will test whether the drug PV-10 works better in patients with a distinct immune biomarker signature in both blood and tumor tissue.