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!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
21.08.2017 | Materials Sciences
21.08.2017 | Health and Medicine
21.08.2017 | Materials Sciences