Dr. Antoni Ribas
A researcher at UCLA’s Jonsson Comprehensive Cancer Center has helped develop a combination drug therapy that shows promise in extending the lives of people with metastatic melanoma. This new therapy also accomplishes this without the side effect of a secondary skin cancer seen in some patients prescribed only one of the drugs.
An estimated 70,000 new cases of melanoma are diagnosed each year in the United States. Of those, 8,000 people will eventually die of the disease, when the cancer spreads to other parts of their bodies. About half the people with this metastatic melanoma, or 4,000 people a year, have a mutated protein called BRAF mutation.
In the new study co-authored by Dr. Antoni Ribas, UCLA professor of medicine and a member of the Jonsson Cancer Center, researchers found that the BRAF mutation gives melanoma the signal to grow continuously as a cancer.
This mutation can be treated with the recently FDA-approved drug Zelboraf. But Zelboraf taken by itself cannot completely block that signal. The study showed that when the experimental drug cobimetinib is added, the combination slows the growth of the melanoma.
The study was published online by The New England Journal of Medicine, and will appear in its November print edition.
Researchers had previously discovered that 25 percent of patients who’d been given Zelboraf alone had developed a secondary cancer.
“We wondered why it was that we were getting the melanoma to shrink, but another skin cancer was developing,” Ribas said.
In addition to combining cobimetinib with Zelboraf also decreased incidence of secondary skin cancer, the study showed.
The scientific basis of this combination is based on prior studies by Dr. Roger Lo, associate professor of medicine specializing in dermatology and JCCC member, who had described the mechanisms of how melanoma became resistant to Zelboraf and how the addition of a drug like cobimetinib would prevent melanoma from becoming resistant to the drugs.
Results of the study also showed the drug combination extended the duration of response to the drug from a median of six months with Zelboraf alone to nine months with the combination.
“Now we’ve demonstrated the significantly increased duration of response to the therapy,” Ribas said.
Ribas collaborated with 18 researchers from the United States, Europe, Australia and Russia as last author of the study.
The data was collected internationally during a one-year period. Four-hundred-ninety-five patients participated at 135 sites in the United States, Australia, New Zealand and Europe. Zelboraf was administered twice daily, in combination with cobimetinib which was taken once a day for 21 days, followed by seven days off.
Additional results saw that 20 percent of patients still suffered from some side effects, like diarrhea, rash, fatigue and edema while taking both drugs.
The next step for the researchers is to seek FDA approval for cobimetinib in combination with Zelboraf, in the hopes that patients with BRAF mutated metastatic melanoma will be able to benefit from the drug combination.
The findings were presented during the 2014 European Society for Medical Oncology conference in Madrid, in late September.
- Reggie Kumar