Nivolumab Combined with Radiation Therapy May Be New Treatment Option for Patients with Melanoma Brain Metastases, Say Moffitt Cancer Center Researchers

“President Jimmy Carter’s battle with metastatic melanoma to the brain has placed increased attention on management of this disease. President Carter was treated with focused stereotactic radiation to the brain and anti-PD-1 therapy. Researchers at Moffitt Cancer Center recently reported the first series of patients treated with this combined modality approach. They found that radiation therapy combined with the immune-targeting drug nivolumab in melanoma patients with brain metastases is safe and improves their survival compared to historical data.

“Nivolumab is a therapeutic agent that targets a protein on immune cells called PD-1. Binding of PD-1 to its ligand PD-L1, which is found on tumor cells, causes immune cells to decrease their activity and allows cancer cells to escape immune detection and cell death.  Nivolumab blocks the PD-1/PD-L1 interaction and restimulates the body’s own immune system to target tumor cells. Nivolumab has been approved by the Food and Drug Administration to treat advanced non-small cell lung cancer, renal cell carcinoma, and melanoma; however, the impact of nivolumab on brain metastases is unclear.”


Opdivo Plus Yervoy Gets FDA OK for Melanoma

“Indications for the blockbuster cancer drug nivolumab (Opdivo) have expanded again, as the FDA has approved the anti-PD-1 antibody in combination with ipilimumab (Yervoy) for treatment of unresectable or metastatic melanoma.

“The indication includes both BRAF-wild type and BRAF-mutant melanoma. At the same time, the FDA expanded the indication for single-agent nivolumb to include patients with previously untreated BRAF-wild type melanoma.

“Granted by the FDA’s accelerated approval process, the indication is the seventh for nivolumab, both indications leave the door open for the FDA to request confirmatory data or clinical trials. The approvals increase the number of nivolumab indications to seven, including four in melanoma, all granted since late 2014.”


NICE Draft Guidance Recommends Nivolumab for Advanced Skin Cancer

“NICE recommends that nivolumab (also called Opdivo, and manufactured by Bristol Myers Squibb) is made available on the NHS as a treatment option for patients with advanced (unresectable or metastatic) melanoma.

“The independent Committee decided that a consultation on the draft recommendations was not needed for this appraisal, so the recommendations could go straight to a final appraisal determination (FAD). This happens when the Committee recommends a treatment in line with its licence.

“Professor Carole Longson, Health Technology Evaluation Centre Director said: ‘We are pleased to be able to recommend nivolumab for treating advanced skin cancer in final draft guidance. In 2011, over 13,000 people were diagnosed with melanoma in the UK, and it accounts for more deaths than all other skin cancers combined. I am sure this will be welcome news to patients and healthcare professionals alike.’ ”


Experts Grapple With Nuances of Navigating New Frontier in Melanoma

“Emerging data showing improved survival with targeted and immunotherapeutic approaches are rapidly altering the standard of care for patients with melanoma. For BRAF-positive patients with metastatic or unresectable melanoma, the standard of care includes a BRAF inhibitor in combination with a MEK inhibitor. For patients with or without BRAF mutations, there are immunotherapeutic options available in frontline and in resistant disease settings.

“Questions remain, however, in terms of how to optimally sequence and/or combine both targeted agents and immunotherapies. And, for BRAF-mutant disease, when is it appropriate to switch from a targeted approach to an immunotherapeutic one?”


The Growing Arsenal of Immunotherapy Drugs for Melanoma


Large numbers of immune cells (T cells in particular) are frequently found within or adjacent to melanoma tumors, indicating that the tumors attract the attention—if not the action—of the immune system. True to its reputation as one of the most ‘immunogenic‘ cancers, melanoma now has more U.S. Food and Drug Administration (FDA)-approved immunotherapy (immune system-targeting) drugs than any other cancer type. As a consequence, metastatic melanoma is no longer the universally fatal disease it was even just 3 or 4 years ago. Continue reading…


Biopsy-Free Detection of Melanoma Metastasis

“According to the results of a new study, a new imaging technique is able to detect the distant spread of melanoma to the lymph nodes, which could help patients avoid potentially risk surgery. Researchers tested the non-invasive technique in a first-in-human study as a potential alternative to standard lymph node surgery.

“The results, from researchers at the University Hospital Essen and the University of Duisburg-Essen in Germany, are published in Science Translational Medicine.

“The novel audio-visual approach used to image patients with melanoma both ex vivo and in vivo significantly improved the tumor metastasis detection rate in excised sentinel lymph nodes compared with standard protocols (22.9% vs 14.2%).”


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.”