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.”


Melanoma Brain Metastases: Q&A With Keith Black, MD

“Malignant melanoma is one of the most common primary tumors to spread to the brain. In close to 50% of patients who have metastatic melanoma, the disease can be found in their brain.

“For example, in former President Carter’s case, the cancer was first found in his liver and later removed. During his press briefing last month, he announced that the melanoma had metastasized to his brain, and he was beginning treatment with pembrolizumab immediately.

“In order to learn more about melanoma metastases to the brain, Targeted Oncology interviewed Keith Black, MD, chairman and professor, Department of Neurosurgery, Cedars-Sinai Medical Center, director, Maxine Dunitz Neurosurgical Institute, director, Johnnie L. Cochran, Jr, Brain Tumor Center, and Ruth and Lawrence Harvey Chair in Neuroscience.”


Frequency of Certain Immune Cells in Blood May Predict Metastatic Melanoma Response to Pembrolizumab

“Among patients with metastatic melanoma treated with the immunotherapy drug pembrolizumab (Keytruda), those whose cancer responded to the treatment had a higher frequency of immune cells called T cells that were positive for the proteins CD8, PD-1, and Bim (CD8+PD-1+Bim+ T cells) in blood samples taken immediately before starting pembrolizumab than those who had disease progression, according to data presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, held Sept. 16–19.

“Pembrolizumab, which targets the protein PD-1, was approved by the U.S. Food and Drug Administration for treating metastatic melanoma in September 2014. Some patients with metastatic melanoma have remarkable responses to pembrolizumab, whereas others do not respond at all, according to Roxana S. Dronca, MD, a medical oncology consultant and assistant professor of oncology at the Mayo Clinic in Rochester, Minnesota.”


Video: Efficacy of PD-1/PD-L1 Inhibitors in Melanoma

“Jason J. Luke, MD, FACP, assistant professor of medicine, The University of Chicago, discusses the efficacy of PD-1/PD-L1 inhibitors in melanoma. The combination of these inhibitors, nivolumab and ipilimumab, was used to treat patients with previously untreated, unresectable or metastatic melanoma, in the Checkmate 069 study.

“Luke says PD-L1 is very complex and difficult when developing immunohistochemical assays. Since several pharmaceutical companies conduct different assays that test various things, a particular patient may be positive in one case, but not in another. For this reason, patients become very confused.

“Luke also mentions that there is no validated method across the board, so it is difficult to determine the next steps going forward.”


What Determines Whether a Melanoma Patient Will Respond to Checkpoint Blockade Drugs?


Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…


European Commission Approves Pembrolizumab for Advanced Melanoma

“The European Commission has approved the PD-1 inhibitor pembrolizumab (Keytruda) as a treatment for adult patients with unresectable or metastatic melanoma in the first-line and previously treated settings, based on data from 3 clinical trials that assessed the medication in more than 1500 patients.

“The European Commission decision follows a recommendation from Committee for Medicinal Products for Human Use, and allows for the medication to be marketed across 28 European Union member states. The medication is approved at a dose of 2 mg/kg every 3 weeks. In the 834-patient phase III KEYNOTE-006 study, pembrolizumab demonstrated an extension in overall survival (OS) and progression-free survival (PFS) compared with ipilimumab. Additionally, in the 540-patient phase II KEYNOTE-002 study, pembrolizumab improved PFS versus chemotherapy, with OS data pending maturity.

“ ‘Today’s European approval supports our goal of accelerating immuno-oncology research for the benefit of patients around the world,’ Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, said in a statement. ‘We believe that the broad data set supporting this approval helps illustrate the significant potential of Keytruda to treat advanced melanoma, a devastating disease.’ “


New Collaboration Leads to Combo Experimental Therapy for Metastatic Melanoma

“Pharmaceutical companies are teaming up to combine experimental therapies that may help combat metastatic cutaneous and uveal melanomas in a whole new way. The novel international collaboration may bring new combined targeted therapies to the market much sooner.

“Eli Lilly and Immunocore Limited are collaborating in immunotherapy-based clinical trials to evaluate the utility of Immunocore’s lead T-cell receptor-based investigational drug IMCgp100. This agent will be combined with Lilly’s galunisertib (LY2157299) and merestinib (LY2801653) for melanoma treatment. The investigators will explore the durability and efficacy of potential combined regimens in patients with metastatic cutaneous and uveal melanomas.

“ ‘Combining our ImmTAC, IMCgp100 with Lilly’s galunisertib and merestinib has the potential to transform the treatment of metastatic cutaneous and uveal melanoma. Immunocore is committed to the development of IMCgp100 in metastatic uveal and cutaneous melanoma where there is such great unmet medical need,’ said Eliot Forster, who is chief executive officer of Immunocore, Oxford, England.”