April 19, 2016

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)
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 on two new studies showing that the medications, which marshal the body’s own immune defenses, are now having some effect against recurrent, difficult-to-treat head and neck cancer and an extremely lethal skin cancer called Merkel cell carcinoma. The diseases can be caused by viruses as well as DNA mutations, and the data show that the drugs help the immune system to recognize and attack cancers resulting from either cause.

The new studies appear to be the first to find that “virus-driven cancers can be amenable to treatment by immunotherapy,” said Paul Nghiem, an investigator with the Fred Hutchinson Cancer Research Center in Seattle who led the skin-cancer study. Since viruses and other pathogens are responsible for more than 20 percent of all cancers, “these results have implications that go far beyond” Merkel cell carcinoma.

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.

[Long-term survival rates increase for patients treated with immunotherapy]

“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.”

[In-depth: Sean Parker, Silicon Valley’s bad boy genius, on his new $250m institute for cancer immunotherapy]

Scientists don’t know why some patients benefit from immunotherapy and others don’t. In many 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.

How cancer can be tackled with immunotherapy
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Researchers say that new immunotherapy drugs are showing significant effectiveness in battling a range of cancers. (The Parker Foundation)
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.

[Cancer experts named to advise Obama administration on “moonshot” effort]

The trial on head and neck cancer involved patients who had recurrent or metastatic squamous cell carcinoma that didn’t respond to previous treatments, including platinum-based chemotherapy. Head and neck cancer can be caused by the human papillomavirus, or HPV. Data released as an abstract Tuesday showed the immunotherapy drug Opdivo led to improved survival.
Previously, there was no treatment for this particular group of patients that extended life, said Maura Gillison of the Ohio State University Comprehensive Cancer Center, who led the study. “This is the first time in my career that I have had an agent to reach for,” she said.

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 with 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 26 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, Nghiem 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’s 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 at Seattle Cancer Care Alliance 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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