In immunotherapy, T-cells from a cancer patient can be genetically engineered to be specific to a tumor. Dendritic cells (lower left) are special cells that help the immune system recognize the cancer cells and initiate a response. Drugs called "checkpoint inhibitors" also can spur the immune system. (Science Source)
The list of cancers being taken down by immunotherapy keeps growing
NEW ORLEANS -- New immunotherapy drugs are showing significant and extended effectiveness against a broadening range of cancers, including rare and intractable tumors often caused by viruses. Researchers say these advances suggest the treatment approach is poised to become a critical part of the nation's anti-cancer strategy.
Scientists reported Tuesday that the medications, which marshal the body's own immune defenses, are now proving effective against difficult-to-treat head and neck cancer and an extremely lethal skin cancer called Merkel cell carcinoma. Both can be caused by viruses as well as DNA mutations, and the drugs help the immune system to recognize the virus-associated cancer and attack it.
Since pathogens are responsible for more than 20 percent of all cancers, "these results have implications that go far beyond a rare cancer" like Merkel cell carcinoma, said Paul Ngheim, an investigator with the Fred Hutchinson Cancer Research Center in Seattle who led that study.
The new data, plus research released Sunday that showed sharply higher survival rates among advanced-melanoma patients who received immunotherapy, is prompting growing, albeit guarded, optimism among researchers attending the American Association for Cancer Research annual meeting here. In addition to melanoma, the infusion drugs already have been approved for use against lung and kidney cancers.
"We are in the midst of a sea change in how we are treating cancer," said Louis Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center, who wasn't involved in the studies. "We're really seeing the fruits of many years of research into what drives cancer and how it interacts with the immune system to defeat it and survive."
The latest findings, as well as hundreds of ongoing clinical trials across the country, suggest that immunotherapy could be beneficial for more than two dozen kinds of cancer -- and maybe many more. One of the most prominent patients is former president Jimmy Carter, who last year was diagnosed with advanced melanoma that had spread to his brain. He was treated with one of the new drugs, Keytruda, as well as radiation. The combination worked so well, causing his tumors to disappear, that he was able to stop treatment in March.
"What's happening to Jimmy Carter is happening to many, many people," Weiner said.
At the same time, however, researchers caution that they have a long way to go in fully understanding the therapy and transforming it into a viable treatment for a majority of patients. "This period for immunotherapy is comparable to the 1960s for chemotherapy, when we were just beginning to use it," said Roy Jensen, director of the University of Kansas Cancer Center. "There is so much to do and to figure out. We're just at the start of this."
Scientists don't know why some patients benefit from immunotherapy and others don't. In some trials, for example, less than a third of patients have had a positive response. Researchers think that proportion can be increased by combining these "checkpoint inhibitor" drugs -- three have been approved by the government, with several more in development -- or by adding conventional treatments such as chemotherapy, radiation and surgery. Yet much work is needed on how exactly to do that and on how to better comprehend cancer's wide range of defenses.
The research successes are emerging just as the Obama administration, as well as private philanthropists, focus on ways to radically accelerate progress against cancer. Former New York mayor Michael Bloomberg and tech billionaire Sean Parker have announced that they will invest hundreds of millions of dollars in immunotherapy research. On Wednesday, Vice President Biden will address the conference about the Obama administration's anti-cancer "moonshot" initiative.
Head and neck cancer, a devastating disease that affects the patient's ability to eat, breathe and talk, can be caused by the human papillomavirus, or HPV. Data released as an abstract Tuesday showed the immunotherapy drug Opdivo led to improved overall survival for patients with advanced cancer who had not responded to chemotherapy. Such benefit had not been seen before, according to Maura Gillison of the Ohio State University Comprehensive Cancer Center, who led the study.
The scientists divided 361 patients into two groups: One got Opdivo, and the other received chemotherapy selected by individual researchers. At the end of a year, 36 percent of the Opdivo patients were still alive, compared to 17 percent of the chemotherapy group. The immunotherapy drug was beneficial regardless of whether a patient had been infected with HPV.
Gillison said she hoped that the results would establish Opdivo "as a new standard of care option for this patient population and thereby fulfill a huge unmet need."
With Merkel cell carcinoma, which almost always kills quickly, many more cases are triggered by a common virus than by exposure to ultraviolet light. And in the trial, slightly more than half of the 25 Keytruda-treated patients had a significant reduction in their tumors. The drug prompted the immune system "to get up out of its rocking chair" and go attack the cancer, Ngheim said. More than 80 percent of the patients who responded are still experiencing "excellent disease control" six months after starting treatment, and several patients have no sign of disease, he added. The study was published online Tuesday in the New England Journal of Medicine.
Suzanne Topalian, a co-leader of the study and associate director of Johns Hopkins' new Bloomberg-Kimmel Institute for Cancer Immunology, said the results provide an "open door" for considering immunotherapy for other cancers caused by viruses.
Stan Collender receives an immunotherapy drug as part of his treatment for rare Merkel cell carcinoma. (Robert Hood/Fred Hutch News Service)
Stan Collender, a long-time Washington budget expert and public relations executive, was facing the typically dire prognosis when he was diagnosed with Merkel cell carcinoma in 2012. He had three recurrences, with tumors under his chin and in his brain and chest. "I was convinced I was going to die," he recalled recently.
Then in 2015, Collender became one of the patients enrolled in Nghiem's trial. Last spring, he began flying to Seattle every three weeks to get a 30-minute infusion of Keytruda. A few months later, the doctors got the first scans of his body and brain. His oncologist at Hutchinson texted him the news: "Your scans look fantastic..."
That was almost 10 months ago, and the 64-year-old Collender said he now feels "miraculously well." He has gone "from not being able to stop thinking about my cancer to not thinking about it at all."
Collender is hoping the benefit will last. "Is it durable? I don't know," he said. "I'm still a test pilot."
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A New Cancer Drug Shows Even More Promise
Longer term data extends the good news about the immunotherapy drug that stopped Jimmy Carter’s cancer
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.
VIDEO: http://time.com/4298549/cancer-immunotherapy-pembro-drug-melanoma/?xid=gonewsedit&google_editors_picks=true
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.
VIDEO: http://time.com/4298549/cancer-immunotherapy-pembro-drug-melanoma/?xid=gonewsedit&google_editors_picks=true
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.”
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