Immune System-Activating Drugs in Combination Treatments May Be Next Big Thing for Melanoma


Among solid tumors, the curative potential of immunotherapies has been explored most in melanoma. One reason for this is that melanoma tumors often contain so-called immune infiltrates—patches of T cells, the killer cells of the immune system. It seems that these fighter cells arrive at the ‘battlefield’ to target tumor cells for killing, but instead become ‘frozen,’ unable to attack.  How to activate the tumor-killing potential of T cells has been an area of intense and fruitful research, leading to the development of several immunotherapy drugs. Continue reading…


New Standard in Melanoma: Combo of BRAF and MEK Inhibitors

The gist: Two new, similar melanoma treatments have been tested in clinical trials—research studies with volunteer patients. Both of the trials are focused on people with advanced melanoma whose tumors have mutations in the BRAF gene. Such patients are often treated with a targeted therapy called a BRAF inhibitor, but their tumors often become resistant and keep growing. In these two trials, the researchers hope that combining BRAF inhibitors with other targeted drugs known as MEK inhibitors might help patients avoid resistance. One of the trials tested a combination of the drugs vemurafenib and cobimetinib. The other trial combined dabrafenib and trametinib. In both trials, patients treated with the combination treatment fared better than patients treated with just a BRAF inhibitor alone.

“For patients with advanced melanoma that isBRAF-mutation positive, the combination of a BRAF and MEK inhibitor works better than a BRAF inhibitor alone. The data come from 2 phase 3 trials presented here at the presidential session of the European Society for Medical Oncology (ESMO) Congress 2014.

“Experts here say that such combinations should be the new standard of care in this patient population, which accounts for about 40% of all melanoma.

“At present, the first-line treatment for these patients is a BRAF inhibitor used alone, but while these drugs can elicit dramatic responses, they do not last, and after about 5 or 6 months, patients relapse. The tumor develops resistance to the drug via the MAPK pathway, and this is blocked by a MEK inhibitor. Adding a MEK inhibitor to the BRAF inhibitor from the beginning of treatment blocks this resistance pathway and improves outcomes.

“The 2 new trials are known as COMBI-v and coBRIM.

“Both studies used vemurafenib (Zelboraf, Roche/Plexxikon) as the single BRAF inhibitor, but each used a different combination of BRAF and MEK inhibitor.”


Targeted Combination Therapy Halts Disease, Extends Life in Advanced Melanoma Patients

The gist: Researchers tested a new melanoma treatment in a clinical trial—a research study with volunteer patients. The treatment combines the targeted drugs dabrafenib and trametinib. All of the patients who participated in the trial had inoperable stage IIIC or stage IV melanoma. Also, each patient’s tumors had one of two particular mutations in the BRAF gene, known as V600E and V600K. In the trial, patients who were treated with the combination therapy had significantly lower chances of their cancer worsening and lower chances of death.

“A world-first study in today’s New England Journal of Medicine heralds the efficacy of a targeted combination drug therapy after reporting major declines in the risk of disease progression and death in people with metastatic melanoma.

“The multi-centre, double-blind, randomised, phase 3 trial compared oral dabrafenib (150 mg twice daily) and oral trametinib (2 mg once daily) combination therapy with oral dabrafenib (150 mg twice daily) and placebo.

“All trial patients had inoperable stage 3C or 4 metastatic melanoma that had a BRAF gene mutation V600E or V600K. Among cancer patients with metastatic melanoma, about 40 per cent have a BRAF gene mutation – an abnormality that assists some melanoma tumours to grow and spread.

“Led by Associate Professor Georgina Long of Melanoma Institute Australia at the University of Sydney, the finding affirms accumulating evidence of the efficacy of targeted combination therapies in extending life and halting disease progression in patients with cancers that carry genetic mutations that resist monotherapies.”


New Treatment for Melanoma of the Eye Could be Game Changer


Uveal (ocular) melanoma is a difficult-to-treat type of melanoma found in the eye. Remarkably resistant to chemotherapy and prone to metastasis, it is often treated with surgery and/or radiation. Earlier this year, I wrote about new scientific findings that could lead to new targeted treatments for uveal melanoma. These would take advantage of abnormal molecular characteristics of tumor cells. Now, another targeted drug called selumetinib has entered the spotlight. It was recently tested in patients in a clinical trial with promising results. Continue reading…


GSK's Melanoma Study Stopped Early on Survival Boost

The gist: In the U.S. and Australia, oncologists are allowed to prescribe a treatment that combines the drugs Mekinist (trametinib) and Tafinlar (dabrafenib) for people with unresectable or metastatic melanoma whose tumors have a V600E or V600K mutation in the BRAF gene. European regulators would like to see more data on the benefits and risks of the treatment before approving it for European patients. The company that produces the treatment was conducting a clinical trial with volunteer patients to capture that data, but has now decided to halt the trial, which was comparing the combo treatment to the drug Zelboraf (vemurafenib). The trial found that the combo treatment has such a significant improvement on patient survival that the patients who had been taking vemurafenib for comparison should be allowed to switch to the combo treatment, and the trial ended early.

“GlaxoSmithKline has stopped a Phase III study of its combination therapy for advanced cutaneous melanoma ahead of schedule after it showed a significant survival benefit.

“The UK drug giant said an Independent Data Monitoring Committee (IDMC) has made the recommendation as it emerged patients with metastatic melanoma – carrying a BRAFV600 mutation – who took a combo of Mekinist (trametinib) and Tafinlar (dabrafenib) demonstrated an overall survival benefit compared to those taking vemarufenib.

“Safety signals were also good, remaining consistent with that for the MEK inhibitor and BRAF inhibitor observed to date, the firm said.”


European Commission Approves Mekinist for Metastatic Melanoma

“The European Commission has given marketing authorization for trametinib as monotherapy for unresectable or metastatic melanoma in adults with a BRAF V600 mutation, GlaxoSmithKline announced.

“Trametinib (Mekinist), a kinase inhibitor that targets MEK1/MEK2 activation and kinase activity, has not demonstrated clinical activity in patients who have progressed on a prior BRAF inhibitor therapy. Before taking trametinib, patients must have confirmation of a BRAF V600 mutation using a validated test.”

Editor’s note: The European Commission (the executive body of the European Union) has approved the drug trametinib (brand name Mekinist) as a treatment for unresectable or metastatic melanoma in adults whose tumors have a mutation called V600 in the BRAF gene. The approval is based on promising results for the drug in a clinical trial.


ASCO 2014: Highlights for People Dealing with Melanoma


Every year, new cancer treatment insights are shared at the American Society of Clinical Oncology (ASCO) Annual Meeting. Here are some of the most notable recent developments in melanoma treatment, gleaned from researchers’ presentations at ASCO last month: Continue reading…


Combination Dabrafenib/Trametinib Increased PFS in BRAF-Positive Melanoma

“Data from a phase 3 trial demonstrate combination dabrafenib and trametinib was superior to dabrafenib plus placebo for improved PFS in patients with BRAFV600-positive metastatic melanoma, according to data presented here at the ASCO Annual Meeting.

“ ‘This is the first melanoma trial, phase 3, to have an active control arm,’ researcher Georgina V. Long, BSc, PhD, MBBS, FRCP, oncologist at Melanoma Institute Australia at the University of Sydney, said of the COMBI-D trial.”

Editor’s note: This story describes the results of a clinical trial, in which volunteer patients are help test a new treatment. The treatment consists of a combination of the targeted therapy drugs dabrafenib and trametinib. Patients treated with the combination lived longer without progression of their cancer than patients who received dabrafenib plus a non-active placebo. Importantly, these results are specific to patients whose tumors have “BRAF V600E” mutations, which doctors can detect via molecular testing.


UPDATE 1-EU Agency Backs Approval of New GlaxoSmithKline Melanoma Drug

“GlaxoSmithKline’s melanoma drug Mekinist – one of several drugs being sold to Novartis under an asset swap deal – has been recommended for approval by European regulators.

“The European Medicines Agency (EMA) said on Friday its experts had backed the drug, also known as trametinib, as a treatment for unresectable or metastatic melanoma in patients with a mutation of a gene known as BRAF.”