“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.
“Accounting for approximately half of all cancers in the United States, skin cancer is widely recognized as the most common cause of cancer nationwide. More than 3.5 million cases of skin cancer are diagnosed each year, and according to the Skin Cancer Foundation, incidences of skin cancer outnumber all combined cases of breast, colon, lung and prostate cancers.
“With the month of May designated as National Skin Cancer Awareness Month, HemOnc Today highlights 10 issues for oncologists and dermatologists to consider for their patients, as well as the new guideline revisions and research regarding the identification, treatment and management of patients with melanoma and skin cancer.”
Immunotherapy may be patients’ biggest hope for transforming cancer treatment. This approach boosts a patient’s own immune system to fight cancer. More and more immunotherapy treatments are showing promise for more and more patients, and Science magazine named immunotherapies 2013’s Breakthrough of the Year. Continue reading…
“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.”
“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.
“Half of melanoma patients with the BRAF mutation have a positive response to treatment with BRAF inhibitors, but nearly all of those patients develop resistance to the drugs and experience disease progression.
“Now, a new preclinical study published online ahead of print in the Journal of Clinical Investigation from Penn Medicine researchers found that in many cases the root of the resistance may lie in a never-before-seen autophagy mechanism induced by the BRAF inhibitors vermurafenib and dabrafenib. Autophagy is a process by which cancer cells recycle essential building blocks to fuel further growth. Block this pathway with the antimalarial drug hydroxycholoroquine [sic] (HCQ), the authors found, and the BRAF inhibitors will be able to do their job better…
“Based on these promising preclinical results, Dr. Amaravadi and his team have already launched a clinical trial for patients with advanced BRAF mutant melanoma to see how well-tolerated HCQ is with the BRAF inhibitor vemurafenib. ‘So far,’ he said, ‘we are seeing a benefit to patients and low toxicity.’ “
“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
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 on the 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.