Video: Dr. Omid Hamid on Vemurafenib and Atezolizumab in Melanoma

“Omid Hamid, MD, Chief, Translational Research and Immunotherapy, Director, Melanoma Therapeutics, The Angeles Clinic, discusses a recent trial investigating the combination of vemurafenib and atezolizumab in melanoma in patients with previously untreated BRAF-positive unresectable or metastatic melanoma.

“The targeted therapy vemurafenib has a great initial response rate and palliative benefit, but does not have long-term durability. Atezolizumab, an immunotherapy, has a low initial response rate, but has the ability to have a high long-term durability, says Hamid.

“With the combination, the toxicities of elevated liver enzymes and rash were initially seen, however the regimen became more tolerable after it was adjusted, says Hamid.”

Click through to watch the video.


Most Experts Not Surprised by Carter's Status

“Former President Jimmy Carter’s announcement that he is free of metastatic melanoma surprised many people but, not most melanoma specialists contacted byMedPage Today.

“With the evolution of modern radiation therapy techniques and targeted drugs, more patients with metastatic melanoma achieve complete and partial remissions, including remission of small brain metastases like the ones identified during the evaluation and initial treatment of Carter. However, the experts — none of whom have direct knowledge of Carter’s treatment or medical records — cautioned that early remission offers no assurance that the former president is out of the woods.”


Anti-PD-1 Agents Superior to Others in Advanced Melanoma

“Immunotherapy targeting the programmed cell death (PD) pathway was associated with better outcomes in patients with metastatic melanoma than any other therapy, a new meta-analysis concludes.

“The meta-analysis was featured in a poster presentation here at the Society for Melanoma Research 2015 Congress.

“Anti-PD-1 agents might be a better choice as a first-line therapeutic option, according to Seongseok Yun, MD, PhD, an internal medicine resident at the University of Arizona Medical Center in Tucson, and Nicole Vincelette, a PhD student from the Mayo Clinic in Rochester, Minnesota.”


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.”