New Drug May Help Immune System Fight Cancer
Early study found tumor reduction in several forms of the disease
Yervoy works early in the immune reaction to wake up T-cells that are essentially napping on the job, Pardoll said. The PD-1 and PD-L1 drugs work later, at the cellular level.
"This is a whole new kind of treatment, and the early data has looked so impressive," Pardoll said. "I think this just reflects the excitement among biotechnology companies and big pharma in this field."
To understand why researchers are excited, it helps to understand how poorly most cancer drugs perform in early trials. A study published in the journal Clinical Cancer Research in August 2005 found that middle-of-the-road response rates for cancer drugs in early trials was just 3 percent, with the best response rate topping out at 18 percent.
Response rates are so dismal in part because doctors usually don't try unproven drugs in cancer patients until they have run out of other options. All the patients in this study had seen their cancer progress despite several prior treatments. Most had seen their cancer spread beyond its original site.
Pardoll said he also has been impressed with the length of time that patients continue to see benefits from the medications in the new study.
"Among the patients that did respond to anti-PD-1, who had been followed for more than a year, roughly two-thirds were still in a response a year out," he said. "That's something you don't see with chemotherapy; you don't see it with current targeted therapies.
"We think this is because the immune system is being re-educated," Pardoll said. "If that's the case, will we be able to discontinue the antibody and have the patient's immune system take over and keep the cancer at bay?"
Although the drugs have great promise, the researchers said they also were keeping an eye on the adverse events they can cause, some of which have been very serious.
PD stands for programmed death, and together the two molecules work to switch off the body's immune response. Blocking one or the other keeps the immune system active, which is good for fighting cancer, but there are also early signs that manipulating this response may have a downside.
Some patients had side effects that researchers believe are caused by autoimmunity -- the body mistakenly attacking its own organs and tissues. Those side effects include lung and liver inflammation, rashes and hypoglycemia (low blood sugar), perhaps because of a problem with the thyroid gland.
In a study published in a June 2012 issue of the New England Journal of Medicine, three patients who were taking an anti-PD-1 drug died from pneumonitis, or inflammation of the lungs.
The researchers said they're working to understand why the drugs seem to be particularly toxic to the lungs and to mitigate their adverse effects.
"We need to be cautious about the toxicities," Herbst said. "It's great that we're making progress, and now we need to go to randomized trials."