Dabrafenib–Trametinib Combination Extended Survival in Metastatic Melanoma

The gist: A recent clinical trial with volunteer patients compared two treatments for metastatic melanoma. It showed that one of the treatments might give longer survival times for people whose tumors have mutations called BRAF V600E or BRAF V600K. This treatment combines the drugs dabrafenib and trametinib. In the trial, some patients were treated with the combination, and some were treated with only the drug vemurafenib (aka Zelboraf). People who took dabrafenib and trametinib lived several months longer than people who took vemurafenib. None of the patients had taken any previous treatments for their melanoma.

“The combination of dabrafenib and trametinib significantly extended OS compared with vemurafenib monotherapy in patients with treatment-naive metastatic melanoma who harbored BRAF V600E or V600K mutations, according to results of a randomized, open-label phase 3 study.

“The regimens demonstrated comparable toxicity profiles, researchers wrote.

“ ‘Together with the previously reported phase 2 and 3 trials of dabrafenib plus trametinib as compared with dabrafenib monotherapy, these data provide clear evidence for the benefit of this combination therapy over BRAF monotherapy in prolonging survival,’ Caroline Robert, MD, PhD, head of the dermatology unit at Institut Gustave-Roussy in Paris, and colleagues wrote.”


Dysfunctional Oxidative Phosphorylation Makes Malignant Melanoma Cells Addicted to Glycolysis Driven by the V600EBRAF Oncogene

Oncogene addiction describes how cancer cells exhibit dependence on single oncogenes to escape apoptosis and senescence. While oncogene addiction constitutes the basis for new cancer treatment strategies targeting individual kinases and pathways activated by oncogenic mutations, the biochemical basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to V600EBRAF in two malignant melanoma cell lines…”


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.


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.


How necessary is a sentinel node biopsy for melanoma?

A new report weighs the pros and cons of a sentinel node biopsy for melanoma patients.


National Cancer Institute Report shows cancer death rates dropping for most but not all cancers

The Annual Report on the status of cancer shows a decline in cancer deaths from major cancers including lung, colorectal, prostate, and breast, but some cancer deaths continue to increase specifically for men with melanoma as well as for those with liver, uterine, and pancreatic cancers.


Sorafenib does not improve survival in metastatic melanoma Phase III Trial Shows

Sorafenib plus chemotherapy did not improve the overall survival of metastatic melanoma patients not previously treated with chemotherapy. The trial results are published in the Journal of Clinical Oncology.


Wound Complications after Inguinal Lymph Node Lower Than Previously Reported Than in Previous Single Institution Trials

Of 281 cutaneous melanoma patients undergoing inguinal lymph node (ILND) dissection, 14% had wound complications, a rate much lower than those reported in previous single institution studies. In a multivariable model, obesity, and diabetes were significantly associated with wound complications. There was no difference in the rate of reoperation in patients with and without wound complications. The study concludes that the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) appears to underreport the actual incidence of wound complications after ILND.