When Jimmy Carter took the drug pembrolizumab to treat his cancer, it had just been approved for people like him: those with advanced melanoma that had spread to other organs, such as the brain, liver and lungs. The Food and Drug Administration (FDA) approved the drug through an accelerated fast-track process even before the full study on its effectiveness was completed because the results from the first few hundred patients who tested it were so positive.
Now, in a report published in JAMA, researchers provide all of the data on all 655 people who participated in the trial and were followed for more than one year. The results justify the FDA’s decision and provide more confidence that pembrolizumab, or Keytruda, may become an effective treatment that people with late-stage melanoma can try at any time in their disease—before or after other therapies including drugs or chemotherapy or radiation.
The study includes information on 655 people with melanoma who were given different doses of pembro. Some had been treated with other therapies before, including the standard antibody drug, called ipilimumab. The researchers, led by Dr. Antoni Ribas, professor medicine at University of California, Los Angeles, found that no matter what the people had been treated with before, all responded well to pembro, although those who had not been exposed to prior therapies did a little better. Among people who were untreated, 45% responded to the drug, which meant they showed some change in their tumors or the number of tumors. After a year, 52% did not show any progression in their tumor growth and 60% were still alive after two years.
Even people who had been treated with standard therapies before benefited; about 33% responded to the drug and 35% showed no progression of their cancer after a year.
Pembro is part of an exciting new class of immunotherapy drugs against cancer that allows the immune system to see and attack tumors as foreign, much in the same way it targets invading bacteria and viruses. Because tumor cells are healthy cells that start to grow abnormally, they are shielded from attack by the immune system. By removing this cloak of protection, drugs like pembro can unleash the full power of the immune system against cancer cells.
“Patients respond to these drugs because their immune system is ready to go, but the tumor is protecting itself,” says Ribas. “For those patients, we just need to unleash the immune system.”
The fact that not every person responded to the drug, however, shows that the system isn’t perfect. Ribas suspects that for some people, more may need to be done than simply removing the cancer cells’ disguise. For some, the immune system may need additional help in finding and infiltrating the cancer cells so they can then destroy them.
For that, he says, combinations of immune-based anticancer drugs might be needed, and drug companies are intensively studying such cocktails now.
They are also intrigued by another possible benefit of drugs like pembro. In a separate study, published in the New England Journal of Medicine, another group of researchers found that pembro can be effective in treating another skin cancer, a rare form called Merkel cell carcinoma that’s caused by a virus.
By uncloaking the Merkel cancer cells, pembro also exposes the foreign virus that has embedded its own genetic material in the host cell’s DNA. That makes the cancer cells even better targets for immune attack, and that’s what Dr. Suzanne Topalian, director of the melanoma program at the Johns Hopkins Kimmel Cancer Center, and her colleagues found. In their small study of 26 people with the disease, 56% responded, and 67% showed no progression of their cancer for six months.
“This opens the question of whether these therapies are going to be effective in a much broader class of cancers, virus-associated cancers that account for more than 20% of cancers worldwide,” she says.
Those include cancers caused by viruses such as HPV, Epstein Barr, some lymphomas and stomach cancers. Topalian hopes to expand the Merkel cell cancer trial and also wants to see other researchers start to test drugs like pembro in these virus-related cancers. “I hope these results will cause the area of immune oncology research to be more robust,” she says. “In the case of Merkel cell cancer, this is a cancer for which we really didn’t have effective therapies before, so this really opens the possibility that this kind of treatment might become the new standard.”