Advanced melanoma patients taking an experimental pill, vemurafenib, developed by Roche and Daiichi Sankyo were 63 percent less likely to die than patients given chemotherapy, according to a new trial presented on Sunday at a meeting of the American Society of Clinical Oncology in Chicago.
Dr. Paul Chapman of Memorial Sloan-Kettering Cancer Center in New York and the study’s lead investigator called the results an “unprecedented level of difference” for patients with advanced melanoma, who typically survive just eight months on current treatments.
In a separate study presented at ASCO, previously untreated people with advanced melanoma treated with Bristol-Myers Squibb’s Yervoy, or ipilimumab, plus chemotherapy lived an average of two months longer than people who got chemotherapy alone.
Yervoy works by spurring the immune system to fight off the cancer. Vemurafenib is designed for use in patients with tumors that have a mutation in a gene known as BRAF that allows melanoma cells to grow. About half of all melanomas have the genetic aberration.
The Roche trial included 675 patients with previously untreated, inoperable late-stage metastatic melanoma with the BRAF mutation.
After a median three months of treatment, vemurafenib patients also had a 74 percent reduction in the risk of cancer progression compared to dacarbazine.
“This is a huge difference,” said Dr. Antoni Ribas, an oncologist at the University of California, Los Angeles, who has studied vemurafenib. “Even if it diminishes over time, who cares?“
Nearly half of patients treated with the Roche drug had tumor shrinkage, compared with 5.5 percent with chemotherapy.
Side effects included skin rashes and joint pain. About 18 percent of patients developed a low-grade skin cancer.
Analysts, on average, have forecast annual vemurafenib sales of $452 million by 2015 and expect Yervoy annual sales of $1.26 billion, according to Thomson Pharma.
Roche expects US and European regulators to decide on approval of its drug before the end of the year.
Bristol-Myers’ Yervoy was approved in March for patients with inoperable or metastatic melanoma, based on a previous study which showed the drug given alone extended survival by four months in patients who had failed other treatments.
“What was interesting about this study was not only was it the second one to show a benefit,” but that the improvement “took place even in the presence of dacarbazine chemotherapy,” Dr. Jedd Wolchok of Memorial Sloan-Kettering Cancer Center in New York, who presented the study at the meeting, said in a telephone interview.
“We worried a lot that chemotherapy could be immunosuppressive,” Wolchok said, noting that that might explain why the average survival benefit was two months instead of four.
“We don’t know what dacarbazine did to the ipilimumab, but we do know even in the presence of dacarbazine, ipilimumab still produced a durable response and extended survival.”
Doctors said taken together the new studies offer new options for patients.
“This is really unprecedented time to have two new approaches to treat advanced melanoma,” said Dr. Lynn Schuchter of the University of Pennsylvania in Philadelphia, a melanoma expert who moderated a panel discussion of the drugs.
“Once you finally understand what is driving the disease we can develop therapies that are more effective,” she said.
She and others expect vemurafenib to be approved this year. Meanwhile, doctors are already working out treatment strategies.
For patients who are stable with slow-growing tumors, Chapman said he would start them off on ipilimumab.
“That is a drug that can take a while to work, so if the person has time I would rather give him essentially two shots on goal rather than one.”
For advanced patients who need a quick response, he would use vemurafenib first.
Schuchter said now the future is going to be to build upon this success and combine therapies.
“Cancer cells outwit us — they are brilliant — and figure out other pathways,” she said.
Bristol-Myers and Roche announced earlier this week a collaboration to evaluate the combination of Yervoy and vemurafenib as a therapy for metastatic melanoma.
More than 70,000 people in the United States and 160,000 worldwide are diagnosed with melanoma each year, according to the American Cancer Society. The five-year survival rate for the aggressive cancer is just 15 percent.
