Metastatic Melanoma: Not Quite Curable…But Getting There


By 2050, the number of deaths due to malignant melanoma in the U.S. could be three times lower than peak levels reached before 1960. Researchers presented the data behind this prediction at the 2017 European Cancer Congress in January.

It is unclear how much of this anticipated decline in deaths can be attributed to the availability of new, effective treatments. However, it is obvious that much-increased awareness of sunlight exposure as the single factor most responsible for the development of skin melanoma has contributed to lower incidence of the disease.

In any case, the armament of treatments available for metastatic melanoma is currently such that this diagnosis has transformed from being almost universally fatal (even just a few years ago) into a being largely treatable. Since 2011, the U.S. Food and Drug Administration (FDA) has approved eight new drugs for melanoma. Continue reading…


Long-Term Survival Possible With MAPK Inhibition in BRAF-Mutant Melanoma

“Long-term outcomes for BRAF-mutant melanoma patients treated with BRAF and MEK inhibitors are influenced by a number of baseline factors including BRAF genotype, gender, and serum lactate dehydrogenase (LDH) levels, according to a new study.

“Treatment of V600 BRAF-mutant metastatic melanoma has improved with inhibition of the MAPK pathway with BRAF inhibitors and MEK inhibitors. But ‘the degree of response and the duration of survival are highly variable,’ wrote study authors led by Alexander M. Menzies, MBBS, of the Melanoma Institute Australia in Sydney. ‘Whether clinicopathologic factors can be used to predict the clinical course of these patients is largely unknown, and there have been few studies examining this issue.’

“The study included 142 consecutive immunotherapy- and MAPK inhibitor–naive patients with BRAF-mutant metastatic melanoma. All were treated either with BRAF inhibitors (111 patients) or with a combination of dabrafenib and trametinib (31 patients), and the median follow-up was 15.7 months. Results were published online ahead of print in Cancer.”


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.


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.


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.


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.


Circulating tumor cells may be predictive for recurrence and survival in melanoma patients

Circulating tumor cells detected in the blood of stage III melanoma patients may be a predictive blood biomarker helpful for deciding which patients could benefit from aggressive adjuvant therapy.