Melanoma doesn’t strike often but it can be deadly when it does: it accounts for only two percent of all skin cancers but causes most skin cancer deaths. Once it has spread from the original tumor site, melanoma is particularly difficult to treat. Chemotherapy, the standard treatment, causes the tumor to shrink in only about 10 percent of the people treated.
The treatment Shaheen and his colleagues tested in the clinical trial caused tumors to shrink in 61 percent of the people treated. In another 22 percent, the tumors disappeared completely. “This is a revolutionary therapy,” Shaheen says. “The efficacy is dramatic for melanoma. More than 70 percent [of people treated] benefit.”
The treatment consists of two drugs, Nivolumab and Ipilmumab. Both are antibodies, which are natural proteins the immune system uses to kill disease-causing invaders. Ipilmumab disables certain receptors, called CTLA-4 receptors, on the surface of melanoma cells. The effect is akin to removing an invisibility cloak; when these CTLA-4 receptors become disabled, the immune system attacks the tumor cells. Nivolumab blocks the PD-1 receptors on the cytotoxic T-cells, allowing the immune system to act against cancer cells. Although both drugs work well on their own, the clinical trial showed that they are especially potent when combined. “By giving the drugs together, you give a much higher benefit to patients,” says Shaheen.
Some of the people taking part in the clinical trial had side effects. “The immune system attacks the cancer cells as a primary target,” explains Shaheen. “But patients can get immune-mediated side effects from these drugs.” The most frequent side effect in the clinical trial was diarrhea, which doctors treated with the steroid drug prednisone. “Prednisone does not suppress the reaction against the tumor,” Shaheen says, so the diarrhea could be managed during the treatment.
The side effects stopped when the treatments stopped, but the tumors stayed away. Some people who took part in the clinical trial are still in full remission. “The cool thing about immune therapy is its durability,” says Shaheen. “For the first time in history, we can talk about a potential cure for a subset of patients with metastatic melanoma.”
About Montaser Shaheen, MDMontaser Shaheen, MD, is an Associate Professor in the Department of Internal Medicine, Division of Hematology/Oncology, at the University of New Mexico School of Medicine. Dr. Shaheen received his medical degree from Damascus University, and then went on to complete his residency and internship at Southern Illinois University School of Medicine, specializing in internal medicine. He completed his fellowship at Indiana University Medical Center, specializing in hematology/oncology. Dr. Shaheen is certified by the American Board of Oncology. He practices at the UNM Cancer Center.
Paper reference“Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma” was published in the April 20 online edition of The New England Journal of Medicine (www.NEJM.org). Authors are: Michael A. Postow, MD, Jason Chesney, MD, PhD, Anna C. Pavlick, DO, Caroline Robert, MD, PhD, Kenneth Grossmann, MD, PhD, David McDermott, MD, Gerald P. Linette, MD, PhD, Nicolas Meyer, MD, Jeffrey K. Giguere, MD, Sanjiv S. Agarwala, MD, Montaser Shaheen, MD, Marc S. Ernstoff, MD, David Minor, MD, April K. Salama, MD, Matthew Taylor, MD, Patrick A. Ott, MD, PhD, Linda M. Rollin, PhD, Christine Horak, PhD, Paul Gagnier, MD, PhD, Jedd D. Wolchok, MD, PhD, and F. Stephen Hodi, MD
About the Clinical TrialThe clinical trial “Study of IDO Inhibitor in Combination With Ipilimumab for Adult Patients With Metastatic Melanoma,” NLG 2103, is open at the UNM Cancer Center. Learn more at https://clinicaltrials.gov/ct2/show/NCT02073123.
About the UNM Cancer CenterThe UNM Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in the state. One of just 68 premier NCI-Designated Cancer Centers nationwide, the UNM Cancer Center is recognized for its scientific excellence; contributions to cancer research; delivery of high quality, state of the art cancer diagnosis and treatment to all New Mexicans; and its community outreach programs statewide. Annual federal and private funding of more than $72 million supports the UNM Cancer Center’s research programs. The UNM Cancer Center treats more than 60 percent of the adults and virtually all of the children in New Mexico affected by cancer, from every county in the state. It is home to New Mexico’s largest team of board-certified oncology physicians and research scientists, representing every cancer specialty and hailing from prestigious institutions such as M.D. Anderson Cancer Center, Johns Hopkins University, and the Mayo Clinic. Through its partnership with Memorial Medical Center in Las Cruces, the UNM Cancer Center brings world-class cancer care to the southern part of the state; its collaborative clinical programs in Santa Fe and Farmington serve northern New Mexico and it is developing new collaborative programs in Alamogordo and in Roswell/Carlsbad. The UNM Cancer Center also supports several community outreach programs to make cancer screening, diagnosis and treatment available to every New Mexican. Learn more at www.cancer.unm.edu.
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