Patients with late-stage lung cancer face a grim prognosis. So do those with mesothelioma, a rare, incurable type of lung cancer usually caused by exposure to asbestos.
Merck & Co.'s hot new immunotherapy drug Keytruda could be a potent new weapon against these fearsome diseases, according to three studies presented in recent days at the American Association for Cancer Research conference in Philadelphia.
Equally exciting, Keytruda is just one in a growing class of drugs that remove an immune system brake that cancer exploits to evade attack. These so-called checkpoint inhibitors are being tested in cancers of the kidney, colon, brain, and other organs.
"What is emerging is the use of these drugs across a whole range of cancer types," said Lynn Schuchter, a University of Pennsylvania oncologist who presented data from an early melanoma trial of Pfizer's experimental checkpoint inhibitor, called tremelimumab.
Barely four years ago, the first of this new generation of immunotherapies - Bristol-Myers Squibb's Yervoy, or ipilimumab - was approved by the Food and Drug Administration to treat late-stage melanoma. Opdivo, or nivolumab, also sold by BMS, was approved last year for metastatic melanoma and, just last month, for advanced non-small cell lung cancer.
The latest studies could give Keytruda, or pembrolizumab, at least a temporary advantage in a market sure to be worth billions of dollars.
In one study - the first head-to-head comparison of checkpoint inhibitors - Keytruda was superior to Yervoy against advanced melanoma. One year after 830 patients began treatment, 74 percent who got Keytruda every two weeks and 68 percent who got it every three weeks were still alive, compared with 58 percent on Yervoy, according to the results, which were also published by the New England Journal of Medicine.
In a study of non-small cell lung cancer, the type that accounts for 85 percent of all lung cancer, Keytruda also demonstrated effectiveness. What's more, the study showed the importance of identifying patients likely to benefit - namely those whose tumor cells produce a lot of a protein called PD-L1, the immune system brake that Keytruda cuts.
Overall, 19 percent of the 495 lung cancer patients saw substantial reduction in their tumors. But among the 313 patients with PD-L1 in at least half their tumor cells, the response rate was nearly 50 percent.
"These results have the potential to substantially change the way lung cancer is treated," said Edward Garon, the University of California-Los Angeles oncologist who led the study.
On Sunday, Merck said it had asked the FDA to expand Keytruda's approval to include lung cancer. The disease kills about 158,000 Americans annually and is the leading cause of cancer-related deaths worldwide.
In contrast, mesothelioma is diagnosed in about 3,000 people a year in the United States. While uncommon, it is so ferocious and hard to treat that patients typically die within a year.
"It's a rare disease, low on the priority list," said University of Pennsylvania oncologist Evan Alley, who led the mesothelioma study. "We were glad that Merck recognized that rare tumors also need to be evaluated."
Although the study involved only 25 patients, Keytruda shrank or halted growth of tumors in 19 of them - 76 percent - for about six months. All of the patients were initially tested to make sure they had PD-L1 on at least one percent of their tumor cells.
"This is just one of the checkpoint proteins that we know are important," Alley said. "There are a number that affect the tumor microenvironment. There are also a whole host of proteins that activate the immune system - the equivalent of pushing the accelerator - and we're seeing data that looks promising with those."
Indeed, in the small Pfizer melanoma study, Schuchter and colleagues showed, for the first time, that combining a cut-the-brakes immunotherapy with one that hits the accelerator can safely elicit a clinical response.
"The takeaway message is it's a safe combination, and you can build on the backbone of one immunotherapy," she said.
A study funded by Bristol-Myers Squibb and presented at the conference bolstered the additive approach; combining the company's Yervoy with Opdivo decreased the risk of melanoma progression or death by 60 percent compared to Yervoy alone.
But the financial implications for the health care system are worrisome, experts say. Yervoy costs $11,000 a month, while newer checkpoint inhibitors are even pricier. It is also unclear how long some of the drugs will work, or need to be given.
Costs aside, patients such as Beth Creelman-Norris, 45, of Drexel Hill can attest to the benefits.
In 2012, the construction project manager had surgery to remove a small, early-stage melanoma from her left cheek and, three months later, one that appeared on her back.
Last year, an innocuous symptom - wheezing - led to the horrifying discovery that the skin cancer had spread to her lungs and neck.
She was treated with Yervoy and radiation at Penn from August through October.
"It helped in my lungs but not on the neck lump," she recalled. "But in September, [Keytruda] was approved. The timing was unbelievable."
A half-hour-long infusion of Keytruda every three weeks beginning in December has reduced her walnut-sized neck tumor to "an M&M size" and helped her lungs. The main side effect was flulike symptoms after the first dose.
"I don't want to be seen as a cancer patient, just a person," said Creelman-Norris, who until now has kept her diagnosis private. "But now I feel so lucky that I want people to know. I'd be ashamed not to be the ambassador of this good news."