New drugs to treat cancer come along pretty regularly, and, to gain approval, each one must outperform the current standard treatment. But the share of patients who respond to a new drug can be modest, and the months of life they gain by using it are, sadly, often counted in the single digits.
Now, there’s hope among researchers and pharmaceutical companies that a drug approved by the Food and Drug Administration (FDA) earlier this month will pave the way toward bigger gains against cancer. The drug, pembrolizumab (Keytruda), is designed to treat melanoma skin cancer, which kills almost 10,000 Americans a year. One in four patients responds to the drug, and many go into a long remission.
Keytruda and others still in the FDA approval pipeline disrupt a process by which cancer cells tell the immune system not to attack them as intruders. The drugs are already being tested on kidney, bladder, and small cell lung cancers and could eventually be used against an even wider range of cancers.
PD-1 Is Pretty Darn Hot
Keytruda and a handful of other drugs that target the same process are “the hottest area in cancer research,” according to Dr. Antoni Ribas, an expert on cancer immunotherapies at the University of California, Los Angeles.
“This is I think the beginning of what will be a fairly significant change in the way that we treat multiple types of cancer in the years and decades to come,” agreed Dr. Evan Lipson, an assistant professor of oncology at the Johns Hopkins University medical school.
Scientists have long known that cancer somehow tricks the immune system in order to grow and spread. About 15 years ago, researchers discovered the PD-1 pathway that is the basis of Keytruda and other new drugs. The work built on research on a separate but related pathway that resulted in the drug ipilimumab (Yervoy).
We can imagine the immune response as like a car at an intersection, looking for a green light telling it to move forward and attack cancer cells, or a red light telling it to remain stopped, Lipson said.
There are a series of lights that calibrate the immune system’s response. Cancer cells have devised ways to turn green lights red, escaping the immune system’s attack. (PD-1, a protein on the surface of T-cells, is one potential red light, turned on by PD-1 ligand, or PDL, on the surface of the cancer cells.) Now scientists have learned to turn those lights green again, unleashing the “tremendous power of the immune system,” Lipson said.
The current optimism comes from observations that green lights on this particular pathway send a lot of cancer-fighting traffic through. And the traffic keeps on coming, so patients remain in remission for longer.
“People have tried to activate anti-tumor immunity in the past, but the approach that seems to work well is to block these paths,” said Dr. Arlene Sharpe, an immunologist at Harvard Medical School.
More PD-1 Drugs Likely on the Way
Keytruda, made by Merck, is the second drug developed to target the PD-1 pathway. The first was Bristol-Myers Squibb’s nivolumab, which is already on the market in Japan as Opdivo, but the company hasn’t yet received the FDA’s okay to sell the drug in the United States. Bristol-Myers Squibb doesn’t think Keytruda is different enough from Opdivo: The company has sued Merck for patent infringement.
The competition among drug companies is good news for patients because it means that more drugs of this type are being researched.
As for why Big Pharma is so keen on anti-PD-1 drugs, the usual suspects are to blame: their price point and the potential size of the market.
Keytruda will sell for roughly $12,500 per patient per month, making it the 6th most expensive drug on the market, according to the trade publication FiercePharma.
More patients will queue up for the drugs for each type of cancer they successfully treat. On their own, they can only free T-cells to fight cancer if the T-cells are already in a cancerous tumor. This is more likely to be true in melanoma, bladder cancer, kidney cancer, small cell lung cancer, and head and neck cancers. Together, those cancers account for at least 300,000 new patients per year in the United States, according to the National Cancer Institute.
Drug manufacturers, doctors, and patients hope that more patients will respond to the drugs if they’re used in combination. Complementary drugs could send more T-cells to the tumor or create more green lights along various immune pathways within the tumor.
“This is a tremendously exciting breakthrough for many of the patients being treated in oncology, and whenever a drug like anti-PD-1 is as successful as it’s been, researchers and pharmaceuticals and patients want to get on board that train and try to maximize the effect of the drug for all of us,” Lipson said.
Even so, introducing new drugs takes time. As of now, only melanoma patients can get Keytruda outside of clinical trials. But because these drugs are so popular, there are clinical trials testing more advances in melanoma treatment and trying anti-PD-1 drugs on patients with other types of cancer.