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Scientists Find New Way to Combat Drug Resistance in Skin Cancer

Scientists Find New Way to Combat Drug Resistance in Skin Cancer | Melanoma Dispatch | Scoop.it

"Rapid resistance to vemurafenib – a treatment for a type of advanced melanoma, the deadliest form of skin cancer – could be prevented by blocking a druggable family of proteins, according to research published in Nature Communications today.


"Scientists at the Cancer Research UK Manchester Institute, based at the University of Manchester, have revealed the MLK family of four enzymes 'undoes' the tumour-shrinking effects of vemurafenib."


Editor's note: This story describes a potential new way to treat melanoma that has become resistant to vemurafenib. While promising, the research is still in preliminary stages, so new treatments are not yet available for patients.

Cancer Commons's insight:

Medical Xpress  |  May 22, 2014

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‘Real World’ Safety Study of Vemurafenib in BRAF V600–Mutated Metastatic Melanoma Shows Similar Safety Profile as Pivotal Trials

‘Real World’ Safety Study of Vemurafenib in BRAF V600–Mutated Metastatic Melanoma Shows Similar Safety Profile as Pivotal Trials | Melanoma Dispatch | Scoop.it

"As reported in The Lancet Oncology by Larkin et al, interim results of a safety study designed to reflect the spectrum of patients encountered in routine practice suggest that vemurafenib (Zelboraf) has a safety profile in patients with BRAF V600–mutated metastatic melanoma similar to that observed in the more select patient population included in registration trials. The study included patients with limited treatment options and sizable proportions with brain metastases, elevated lactate dehydrogenase (LDH), poor performance status, and age ≥ 75 years."


Editor's Note: The important takeaway from this story is that the drug vemurafenib can be used safely and effectively in some melanoma patients with poor prognoses, who may not fit the profile of patients typically enrolled in clinical trials to test the drug. To learn more about clinical trials and "targeted therapies" like vemurafenib, visit our Melanoma Basics.

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The ASCO Post  |  Mar 5, 2014

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Trial Supports Recent US FDA Approval of New Melanoma Combo Treatment

Trial Supports Recent US FDA Approval of New Melanoma Combo Treatment | Melanoma Dispatch | Scoop.it

The US Food and Drug Administration just granted accelerated approval for a treatment that combines two drugs that target melanomas with BRAF mutations — but this was contingent results of an ongoing phase III clinical trial. The drugs are the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist). Now the latest results of the trial are in and they look good. This combination treatment is not approved elsewhere in the world, and the trial included 423 people from Australia, Europe, and North and South America. Final results are expected later this year and will be presented at a scientific meeting. In addition, another trial is comparing this combination treatment to the BRAF inhibitor vemurafenib (Zelboraf), which is also FDA-approved.

Cancer Commons's insight:

GlaxoSmithKline │ Jan 24, 2014

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Vemurafenib Extends Life up to 3 Years in Melanoma Trial

An ongoing clinical trial found that 26% of melanoma patients treated with vemurafenib (Zelboraf®) were alive at 3 years—far longer than the average survival time of 9 months with conventional chemotherapy. Vemurafenib is a BRAF inhibitor and this trial includes 32 people with the most common BRAF mutation (V600E). In addition, 5 people survived at 3 years and 4 months; 3 of them had no evidence of disease. 

Cancer Commons's insight:

Drugs.com | Nov 9, 2012

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Immunotherapy, BRAF Inhibitor Sequence Affected Outcomes in Metastatic Melanoma

Immunotherapy, BRAF Inhibitor Sequence Affected Outcomes in Metastatic Melanoma | Melanoma Dispatch | Scoop.it

"Prior treatment with immunotherapy did not limit response to BRAF inhibitors among patients with metastatic melanoma, according to results of a retrospective study.


"However, patients who underwent initial treatment with BRAF inhibitors and subsequently received immunotherapy with ipilimumab (Yervoy, Bristol-Myers Squibb) demonstrated poorer outcomes, results showed.


"Patients with BRAF-positive metastatic melanoma have several treatment options, including BRAF inhibitors vemurafenib (Zelboraf, Hoffmann-La Roche) and dabrafenib  (Taflinar, GlaxoSmithKline), the MEK inhibitor trametinib (Mekinist, GlaxoSmithKline), and the immunotherapy agents ipilimumab and interleukin-2. Yet, there are limited data with regard to optimal sequencing, according to researchers."

Cancer Commons's insight:

Healio  |  Mar 14, 2014

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Krishan Maggon 's curator insight, March 15, 2014 8:19 AM

Prior treatment with BRAF inhibitors reduced subsequent response to immunotherapy. Prior treatment with ipilimumab had no effect on response to BRAF inhibitors.

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Extended Follow-up in BRIM-3 Shows Prolonged Survival With Vemurafenib in BRAF V600E/K Mutation–Positive Melanoma

Extended Follow-up in BRIM-3 Shows Prolonged Survival With Vemurafenib in BRAF V600E/K Mutation–Positive Melanoma | Melanoma Dispatch | Scoop.it

"In the BRIM-3 trial, vemurafenib (Zelboraf) was associated with improved progression-free and overall survival vs dacarbazine in patients with advanced BRAF V600 mutation–positive melanoma. In an extended follow-up reported in The Lancet Oncology, McArthur et al found that superior survival outcomes were maintained and were present in both theBRAF V600E and BRAF V600K mutation subgroups."


Editor's note: Read more about vemurafenib here: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a612009.html

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The ASCO Post  |  Feb 12, 2014

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Genentech Adds MEK Inhibitor to Phase III BRAF Inhibitor Trial

Biotech company Genentech has added a MEK inhibitor to a phase III trial of vemurafenib, an FDA-approved BRAF inhibitor. MEK inhibitors have been shown to counteract resistance to BRAF inhibitors. The experimental MEK inhibitor is called GDC-0973 and is also known as XL-518 or RG7421. Vemurafenib (Zelboraf®) targets melanomas with BRAF V600 mutations, which are found in about half of these aggressive skin cancers. Genentech is part of the Roche Group and the two companies are conducting this combination treatment trial jointly.

Cancer Commons's insight:

US Securities and Exchange Commission filing │ Jan 14, 2013

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Dabrafenib May Shrink Melanomas in the Brain

An early stage clinical trial suggests that dabrafenib, a BRAF inhibitor, could treat melanomas that have spread to the brain. The study, reported in The Lancet, included 10 people with brain metastases of melanomas that had BRAF mutations. Tumors shrank in 9 patients and were not evident in 4 patients. This is a surprise because the drug had not been expected to cross the blood-brain barrier effectively. Indeed, melanoma patients with brain metastases have been routinely excluded from previous trials of vemurafenib (Zelboraf) and other BRAF inhibitors.

 

Primary source: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970269-3/abstract

Cancer Commons's insight:

MedPage Today | May 18, 2012

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