A new study by researchers at UCLA’s Jonsson Comprehensive Cancer Center (JCCC) describes a new treatment that combines the drug Zelboraf® (vemurafenib) with an experimental drug cobimetinib for metastatic melanoma, a deadly form of skin cancer. The therapy extends patients’ lives and does not expose them to the serious side-effect of a secondary skin cancer. That side-effect occurs in 25% of the patients prescribed Zelboraf alone. The findings were presented during the 2014 European Society for Medical Oncology (ESMO) conference in Madrid, Spain, which took place from September 26 to September 30.
The researchers found that a mutation known as BRAF gives melanoma the signal to grow continuously as a cancer. Zelboraf taken by itself cannot completely block that signal; however, when cobimetinib is added, the combination produces a more robust response. The present study was based on previous studies by Dr. Roger Lo, associate professor of medicine (dermatology) and JCCC member. Those studies described the mechanisms of how melanoma became resistant to Zelboraf and the addition of a drug-like cobimetinib would prevent these mechanisms.
“We wondered why it was that we were getting the melanoma to shrink, but another skin cancer was developing,” explained co-author Dr. Antoni Ribas, UCLA professor of medicine (hematology and oncology) and JCCC member. Approximately 70,000 new cases of melanoma are diagnosed each year in the US. Of those, 8,000 patients will die of the disease. About 50% of patients with metastatic melanoma, or 4,000 individuals a year, have the BRAF mutation and can be treated with Zelboraf. In August 2011, the US Food and Drug Administration (FDA) approved use of Zelboraf.
Dr. Ribas collaborated with 18 other scientists from the United States, Europe, Australia, and Russia. He noted, “Now we’ve demonstrated the significantly increased duration of response to the therapy.” The study findings also revealed that the drug combination extended the duration of response to the drug from an average of six months with Zelboraf alone to nine months with the combination.
Over a one-year period, the data was collected from a number of sites around the globe: 495 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 7 days of no medication. The combination therapy is not free of side-effects: 20% of the study participants suffered from some side effects, such as diarrhea, rash, fatigue and edema while taking both drugs. The researchers plan to seek FDA approval for the combination therapy in the hope that patients with BRAF mutated metastatic melanoma will be able to benefit from it.
UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2014, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 14 years.