Drug Combo Improves Survival In Advanced Melanoma Patients
By C. Rajan, contributing writer
A new study finds that patients with advanced metastatic melanoma survived longer when treated with a combination of an immune system booster and a standard cancer drug. Lead author of the study, Dr. F. Stephen Hodi, designed the study to investigate whether pairing an immune booster with the immune checkpoint blocker would be better able to tackle the cancer, describing the pairing as “pressing the immune system's accelerator while releasing the brake.”
The Phase 2 clinical trial involving 245 patients and conducted by Dana-Farber Cancer Institute researchers paired cancer drug ipilimumab (Yervoy), an immune checkpoint blocker, along with sargramostim, an immune stimulant, on patients with metastatic melanoma. Stage 3 and stage 4 melanoma patients who received the drug combination survived 50 percent longer with a median time of 17.5 months compared to the 12.7 months survival seen in patients who received only the cancer drug.
The one-year survival rate was 68.9 percent in patients receiving the combination versus 52.9 percent in the ipilimumab-only group. Also, patients receiving the combination therapy encountered fewer serious adverse side effects than those who received only the cancer drug.
The study also showed that the median progression-free survival was similar in both patients groups at 3.1 months, which was unexpected, given that overall survival was significantly improved. Hodi explains, "It could be that the treatment is causing inflammation that looked like early disease progression, but we won't know without further studies."
In any case, the improvement in overall survival of almost five months and the lower toxicity observed with the patient group receiving the immune booster is a very promising result. The researchers caution that these results will need to be confirmed with larger trials and longer follow-ups.
Hodi adds, "But this opens the possibility of improving clinical outcomes and decreasing serious side effects in treating advanced melanoma with ipilimumab."
The cancer immunotherapy drug, ipilimumab (Yervoy, Bristol-Myers Squibb) is a monoclonal antibody that targets CTLA-4, a protein receptor which slows down the body’s immune system and keeps it from effectively fighting cancer. Ipilimumab works by blocking CTLA-4, thus allowing the immune system’s T cells to attack and kill the cancer cells. Yervoy is indicated for melanoma and is currently undergoing investigation in clinical trials for other cancers as well.
The immune booster, sargramostim, is a type of natural protein called granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates the immune system by promoting the growth of white blood cells. Sargramostim is commonly used to restore white blood cells in cancer patients who have received a stem cell transplant.
The study is published in the Journal of the American Medical Association.