A cancer drug being developed by Bristol-Myers Squibb reduced the risk of death from advanced melanoma by more than 30 percent in a late stage clinical trial, representing a potential major advance in treating a disease for which there are few options.
Melanoma is one of the deadliest cancers and can quickly spread from the skin to internal organs, such as the brain.
"Once it metastasizes the average survival is six to nine months and we really had no effective treatments for patients who have had prior treatment for melanoma," said Dr Steven O'Day, one of the study's lead investigators.
In the 676-patient study, more than 20 percent of those who took the Bristol drug ipilimumab were alive after two years, with some alive four years after receiving the immunotherapy, according to data presented at the American Society of Clinical Oncology (ASCO) meeting in Chicago.
Triggers T-cells to battle cancer
"I think this a breakthrough for the field of metastatic melanoma that has had a lot of negative Phase 3 trials in the last decade. It's impacting survival, which is the gold standard in cancer clinical trials," said O'Day, director of the melanoma program at The Angeles Clinic and Research Institute in Santa Monica, Calif.
Ipilimumab, a biotechnology drug, helps to activate the immune system's T-cells to fight the cancer. It was administered via a 90-minute infusion every three weeks for a total of four doses.
All patients in the trial had previous treatment for melanoma before getting either an experimental cancer vaccine called GP-100, ipilimumab, or a combination of the two.
The primary goal of the study was survival and both groups that received the Bristol drug had a statistically significant improvement in overall survival compared with those who just got the vaccine, researchers said.
In the two ipilimumab arms the risk of death was reduced by 32 percent to 34 percent over the GP-100 vaccine alone.
Median survival, or the time it took for half the patients to die, went from 6 months on the vaccine to 10 months with the Bristol drug. But for some patients the benefit was far more extensive.
"If you look at one year and two year survival, there was a near doubling of benefit with ipilimumab," O'Day said.
One year survival was seen in 25 percent of the vaccine patients compared with 44 percent on the combination and 46 percent for ipilimumab alone. After two years, 14 percent of vaccine patients were alive versus 22 percent and 24 percent in the Bristol drug arms.
"The longest survival in the 'ipi' arms is 55 months at the time of analysis," O'Day said.
In the 20 percent to 30 percent of patients for whom the drug really works, survival "tends to be months and years, not weeks and months like chemotherapy," O'Day said.
He said a genetic biomarker test was needed to determine just which patients were most likely to benefit from the drug.
Serious side effect risks
Because of the way the drug impacts the immune system it does have some potentially serious side effects.
About two thirds of patients on ipilimumab had some form of immune related side effects compared with one third on vaccine, researchers said.
Most were mild and completely reversible, but about 10 to 14 percent of patients had more severe side effects, such as colitis, that required steroids or immunosuppressive therapy to control the symptoms, O'Day explained.
Some 2 percent to 3 percent of patients on ipilimumab suffered treatment related death due to colon perforation or other severe immune system side effects.
Doctors would have to closely monitor patient reaction, O'Day said, but he added the toxicities could be managed.
O'Day believes that ipilimumab may also work in other types of cancer and expects it will gain U.S. approval.
Leerink Swann analyst Seamus Fernandez forecasts ipilimumab sales of $575 million in 2016 with an approval for metastatic melanoma.
O'Day is counting on that approval.
"We're hopeful that this (data) is the beginning of what will be a rapid regulatory processing to try to get this drug on the market and access to more patients with melanoma," O'Day added.