The eagerly awaited results provide some of the clearest evidence yet that drugs created to pinpoint molecular characteristics of patients’ cancers can produce unprecedented benefits.
“This is really a huge step toward personalized care in melanoma,” said Paul Chapman of the Memorial Sloan-Kettering Cancer Center in New York, who led the study. “This is the first successful melanoma treatment tailored to patients who carry a specific gene mutation in their tumor.”
Chapman and others cautioned that the drug is not a cure and that many patients’ tumors appear to become resistant to the treatment, making it unclear how long it may prolong their lives. But for a disease that has been so difficult to treat, the results are striking.
“This is really unprecedented for patients with melanoma,” said Lynn Schuchter of the University of Pennsylvania, who moderated the panel where the results were presented at the annual meeting of the American Society of Clinical Oncology in Chicago. “It just changes the landscape for patients.”
Conventional chemotherapy usually works by killing any rapidly dividing cells. Because cancer cells proliferate quickly, chemo drugs can shrink tumors. But they also kill healthy cells, which is why they cause nausea, vomiting, hair loss and other often debilitating side effects.
PLX4032 is one of a new generation of drugs that researchers hope will be more effective and less toxic, because they zero in on genetic characteristics of cancer cells that are not found in healthy cells.
“Whereas in the past we had to use a shotgun approach to cancer treatment — treating many to help a few — we now are on the cusp of a new era in cancer treatment where we can use these predictive tests to focus our treatments on those patients who are most likely to respond to a specific cancer treatment,” said J. Leonard Lichtenfeld, deputy chief medical officer at the American Cancer Society.
Melanoma strikes more than 68,000 Americans each year and kills about 8,700. Despite decades of research, it remains one of the deadliest malignancies, with few treatment options.
“This is a very exciting and important study in a disease that for decades has resisted any meaningful treatment when it has spread through the body,” Lichtenfeld said.
About half of melanoma patients’ tumors carry the “V600E” mutation of a gene known as BRAF, which causes skin cells to reproduce out of control. PLX4032 reverses the pernicious effects of that mutation. Early studies indicated that the drug could dramatically aid terminally ill melanoma patients, quickly shrinking tumors and alleviating many symptoms, such as pain and breathing problems.
The new results are the first to show that it could do what doctors had hoped: stave off death. The study involved 675 patients with advanced, inoperable melanoma with the BRAF gene mutation. The patients took either the standard chemotherapy drug dacarbazine or the new drug. After three months, the effectiveness was so stark that the study was stopped so those getting standard chemotherapy could switch.
“For our patients, it was just remarkable,” said Schuchter, who helped enroll patients in the study.
Some patients who were taking powerful painkillers to cope with excruciating pain were able to discontinue their medication. Others who had become dependent on oxygen were able to breath on their own.
The findings were also posted online by the New England Journal of Medicine, along with an editorial by Marc S. Ernstoff of the Dartmouth Medical School. Ernstoff called the drug’s development a “major defining moment that will have an important effect on survival and quality of life” of many patients with melanoma and perhaps other forms of cancer.
Although some patients experienced side effects such as skin rashes and joint pain, they tended to be far less severe than those caused by standard chemotherapy.
Researchers also reported that combining the standard chemotherapy drug dacarbazine with a new compound that simulates the immune system, known as ipilimumab, or Yervoy, improved the chances that advanced melanoma patients would survive.
“This news about vemurafenib is the latest in a positive year for melanoma research, and a significant milestone,” said Suzanne Topalian, chief science officer of the Melanoma Research Alliance and director of the melanoma program at the Johns Hopkins University School of Medicine. “The results also show that targeting a specific genetic mutation in melanoma holds great promise as a therapeutic approach.”