Melanoma's Genetic Trajectories Are Charted in New Study

“An international team of scientists led by UC San Francisco researchers has mapped out the genetic trajectories taken by melanoma as it evolves from early skin lesions, known as precursors, to malignant skin cancer, which can be lethal when it invades other tissues in the body.

“By tracing the genetic changes that take place over time in the development of the disease, the research reaffirms the role of sun exposure in the emergence of precursor lesions, such as the common moles known as nevi, but also suggests that continued ultraviolet radiation (UV) damage to benign precursor lesions may push them on a path toward malignancy.

“More significantly, the study provides new evidence that genetic and cellular characteristics of skin lesions that are neither clearly benign moles nor malignant melanoma place them in a distinctive intermediate category, the existence of which has been hotly debated among dermatologists and pathologists.”


Vemurafenib/Cobimetinib Combo for Melanoma Approved by FDA

“The FDA has approved a combination of vemurafenib (Zelboraf) and cobimetinib (Cotellic) to treat patients with metastatic or unresectable BRAF V600E/K mutation-positive melanoma. The approval was based on based on an extension in progression-free survival (PFS) in the phase III coBRIM study.

“In the data submitted to the FDA, the median PFS with the combination was 12.3 versus 7.2 months with vemurafenib plus placebo (HR, 0.58; 95% CI, 0.46-0.72). PFS was the primary endpoint of the study with secondary outcome measures including overall survival (OS), objective response rate (ORR), duration of response, and safety.”


Targeted Therapy Combinations Still Key in Metastatic Melanoma

“Combinations of targeted therapies continue to advance toward full regulatory approval for patients with metastatic or unresected melanoma, given the substantial benefits seen with these agents. At this time, the FDA is considering two applications for separate combinations of BRAF and MEK inhibiting agents for patients with unresectable or metastatic BRAFV600 mutation-positive melanoma.

“ ‘The future of the treatment of melanoma is clearly going to be in combinations, both for targeted therapy and for immunotherapy,’ said Jeffrey S. Weber, MD, PhD, who recently joined the NYU Langone Medical Center. ‘Already, there is an FDA-approved combination therapy that is targeted; that is dabrafenib and trametinib. There are new combinations coming up, mainly concerning CDK 4/6 and MEK inhibitors in NRAS-mutated but BRAF wild-type melanoma, which is an unmet medical need.’ “


Ipilimumab plus Radiotherapy May Benefit Patients with Metastatic Melanoma

“The combination of ipilimumab and palliative radiation therapy reduced tumor growth and the spread of metastases in some patients with metastatic melanoma, according to prospective, phase 2 study results presented at the ASTRO Annual Meeting.

“Local radiation therapy has the potential to augment the induction of systemic anti-melanoma immune responses when used in combination with systemic anti–CTLA-4 immunotherapy, according to study background.

“Thus, Susan M. Hiniker, MD, instructor in the department of radiation oncology at Stanford University School of Medicine, and colleagues assessed the safety and efficacy of combining ipilimumab (Yervoy, Bristol-Myers Squibb) with palliative radiotherapy in patients with stage IV melanoma. Researchers also assessed the induction of anti-melanoma immune response.

“The analysis included data from 20 patients (men, n = 14) aged 18 to 83 years who had stage IV melanoma. Patients received palliative radiotherapy and 3 mg/kg IV ipilimumab every 3 weeks for four treatment cycles. The radiotherapy was initiated within 5 days of the first ipilimumab treatment at one or two melanoma sites.”


Amgen Receives CHMP Positive Opinion For IMLYGIC™ (Talimogene Laherparepvec)

“Amgen AMGN, +1.94% today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion recommending that IMLYGIC™ (talimogene laherparepvec) be granted approval for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC and IVM1a) with no bone, brain, lung or other visceral disease. If approved by the European Commission, IMLYGIC would be the first in a class of novel agents known as oncolytic immunotherapies.

“IMLYGIC, administered via intralesional injection, is designed to cause the death of tumor cells and to initiate an anti-tumor immune response.”


A Subset of Patients with Metastatic Melanoma Achieves Clinical Benefit from Combination of Immunotherapy and Radiation Therapy

“Immunotherapy combined with palliative radiation therapy (RT) for a subset of patients with metastatic melanoma reduces the growth and spread of the cancer, according to research presented today at the American Society for Radiation Oncology’s (ASTRO’s) 57th Annual Meeting.

“Although melanoma is not the most common type of skin cancer, it is the most serious type. Stage IV melanoma indicates that the cancer has metastasized and spread through lymph nodes to distant sites in the body and/or to the body’s organs. The liver, lungs, bones and brain are areas most frequently affected by these metastatic lesions. Immunotherapy—the use of medicines to stimulate a patient’s own immune system to recognize and destroy cancer cells more effectively—can be combined with other cancer therapies to aid in the treatment of stage IV melanoma. Ipilimumab is an immunotherapy approved for use in melanoma patients.

“This phase II clinical trial is one of the first prospective clinical trials to report results from the treatment of metastatic melanoma with the combination of RT and systemic immunotherapy. In this study, 20 patients with stage IV melanoma were treated with palliative RT and intravenous ipilimumab (3mg/kg) every three weeks, for a total of four treatment cycles. RT was initiated to one or two sites of metastatic melanoma within five days of the initial immunotherapy treatment. All patients had at least one nonirradiated (untreated) site of metastasis that could be used for assessment of response to therapy.”


Surgery on Melanoma That Has Spread into Abdomen More than Doubles Patient Survival Time

“Patients with metastatic melanoma who undergo surgery to remove lesions that have spread into the abdomen live more than twice as long as those treated with drug therapy alone, according to novel new research by a North Shore-LIJ Health System cancer surgeon.

“The study, by North Shore-LIJ surgical oncologist Gary B. Deutsch, M.D., M.P.H., will be presented on Oct. 8 at the 2015 Clinical Congress of the American College of Surgeons in Chicago. Dr. Deutsch’s research is the first comprehensive look at the survival benefits of surgical resection for melanoma metastases in the abdomen since the advent of groundbreaking immunotherapies in recent years that stimulate patients’ immune systems to destroy cancer cells, improving once-dismal survival rates.

“Dr. Deutsch’s study could immediately impact how oncologists across the United States approach metastatic melanoma cases in which the cancer has spread to abdominal organs, he said.”


Nivolumab/Ipilimumab Combination FDA Approved for BRAF Wild-Type Melanoma

“The combination of nivolumab and ipilimumab has received accelerated FDA approval as a treatment for patients with BRAF V600 wild-type (WT) unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study.

” ‘Historically, metastatic melanoma has been a difficult disease to treat. Now, a new treatment option based on the combination of two valued immuno-oncology agents demonstrates significant efficacy versus ipilimumab in metastatic melanoma,’ said Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, in a statement. ‘Today’s approval represents a step forward for the melanoma community, providing hope for patients with metastatic melanoma.’ ”


Combining Two Targeted Therapies Results in Melanoma Patients Living Significantly Longer

“Latest results from a trial of a combination of two targeted therapies (dabrafenib and trametinib) to treat advanced melanoma have shown that patients are living significantly longer on the combined therapy than patients treated with another drug, vemurafenib, when used alone.

“Professor Caroline Robert, of the Institut Gustave Roussy, Paris, France, will tell the 2015 European Cancer Congress today (Monday) that not only is the median overall survival time longer for patients receiving the combination treatment, but also that 51% of patients receiving the combination treatment are alive after two years, compared to 38% of patients receiving vemurafenib alone.

“Analysis of data up to 13 March 2015 showed that the median overall survival time among patients with metastatic melanoma harbouring V600 mutations in the BRAF gene who received the combination treatment was 25.6 months. Among patients receiving vemurafenib alone, it was 18 months. On the basis of this finding, the European Commission approved the combination of dabrafenib and trametinib for use in Europe for these patients on 1 September 2015.”