Investigators from Vanderbilt-Ingram Cancer Center (VICC) and 12 other centers in the United States and Australia have found that a new drug for patients with metastatic melanoma nearly doubled median overall survival.
More than half of patients who were treated with the novel drug vemurafenib, known commercially as Zelboraf, responded to treatment and experienced an impressive median overall survival of nearly 16 months – far longer than the typical survival of just six to 10 months for most patients whose melanoma has spread beyond the initial tumor site.
Results from the Phase 2 trial, led by co-principal investigators Jeffrey Sosman, M.D., director of the Melanoma Program and co-leader of the Signal Transduction Program at VICC, and Antoni Ribas, M.D., professor of Hematology/Oncology at UCLA's Jonsson Comprehensive Cancer Center, were published in the Feb. 23 issue of the peer-reviewed New England Journal of Medicine.
"This study confirms what we have discovered in our earlier trials. Many of our patients are exhibiting a strong, immediate response to this drug and some are living significantly longer, with manageable side effects," said Sosman, professor of Medicine at Vanderbilt University Medical Center. "It was interesting to note that a few of the patients were treated with the drug for up to six months before showing convincing evidence of response."
"This study shows that Zelboraf changes the natural history of the disease," said Ribas. "These results tell us that this drug is having a very big impact, and this changes the way we treat metastatic melanoma."
Approximately half of all patients with metastatic melanoma – the most deadly form of skin cancer – have a BRAF V600 mutation in their tumor. Vemurafenib is an FDA-approved oral drug which works as a kinase inhibitor of the BRAF V600 mutation.
While vemurafenib induced clinical responses in a significant number of BRAF-positive patients when it was approved last year, the initial clinical trials had not followed patients long enough to determine overall survival.
A total of 132 patients with stage IV, BRAF-positive melanoma were enrolled in the Phase II trial. All of the patients had received at least one form of systemic treatment before enrollment in the trial.
Forty-seven percent of patients had a partial response to the drug and six percent exhibited a complete response, for an overall response rate of 53 percent.
Debra Johnson's melanoma had already spread to one of her lungs and her lymphatic system when she was referred to VICC for mutation testing. Her tumor was BRAF-positive and after more than a year on the drug, the wife and mother from New Site, Miss., says her scans are clear and there is no visible evidence of disease.
"This treatment has been an answer to my prayer," said Johnson.
The majority of patients had at least one adverse event related to the drug, but most of these were minor. The most common side effects were joint pain, rash, sun sensitivity, fatigue and hair loss. More than a quarter of the patients (26 percent) also developed cutaneous squamous-cell carcinomas – a less serious form of skin cancer - which were surgically removed.
A Phase III trial of this same drug confirmed significant improvement in both progression-free survival and overall survival with vemurafenib over chemotherapy in an interim analysis. The Phase II study is the first to confirm the durability of the response.
While the clinical trials for vemurafenib have been positive to date, the great majority of patients eventually experience disease progression.
"We are trying to determine what is causing this drug resistance and are searching for new therapies that we can use, perhaps in combination with vemurafenib," said Sosman.
Dagny Stuart | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy