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Lung cancer, which kills almost 160,000 Americans a year, is among the cruelest of foes. Most patients are diagnosed at an advanced stage, undergo punishing chemotherapy and still have a bleak prognosis. More than half die within a year.
Bit by bit, though, scientists are making progress against the nation’s biggest cancer killer. Years ago, they began approaching lung cancer as many different diseases rather than a single one. The 15 percent of patients with certain high-risk mutations, for example, today get “targeted” medications that work better than chemo.
This “divide-and-conquer” strategy, as one researcher describes it, is poised to make an even bigger advance – one that involves the immunotherapy drug used as part of former president Jimmy Carter’s successful treatment for advanced melanoma. It could benefit tens of thousands of patients in the United States alone – as many as a third of those diagnosed at a late stage with the most common form of the disease.
The treatment shift stems from a major international trial in which the drug, Keytruda, beat chemo on both effectiveness and safety in patients who have advanced cancer and a high concentration of a specific protein on their tumors. The Food and Drug Administration last month approved Keytruda as a first-line treatment for such cases, the first time immunotherapy has been given the green light as an initial treatment for lung cancer.
The result is that most new patients now will be tested for the protein, called PD-L1. If they have a high level on their cancer cells, they’ll receive Keytruda rather than chemo, which is much more debilitating, oncologists say.
“We don’t want to oversell this, but for someone like me who has worked in the trenches for years, this is a big deal,” said Julie Brahmer, who led the clinical trial and is the interim director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “I have had one patient on this (drug) for five years, and she has seen her daughter graduate from high school and college.”
It’s decidedly good news in a field where gains are excruciatingly hard to come by and funding lags behind that of many other types of cancer. The National Institutes of Health estimated it would spend $362 million on lung-cancer research in fiscal 2016, compared to almost $700 million for breast-cancer research. Yet lung cancer kills four times more people annually.
Because smoking is the main cause, lung cancer carries a stigma among doctors, the public and patients themselves, studies show. “Patients are sometimes blamed as being responsible for their disease even though we don’t do that to people who are obese or have heart disease or other conditions that may be lifestyle related,” said Albert Rizzo, senior medical adviser to the American Lung Association. “Nobody deserves to have lung cancer.”
The stigma, plus a sense of futility among some physicians, can contribute to the undertreatment of patients with advanced disease. “There’s a lot of nihilism among some community oncologists, who say patients do poorly” on treatments and may not have much experience with newer treatments, including immunotherapy, Brahmer said. She and others say immunotherapy, though not a cure, offers an alternative for certain patients whose only option had been chemo.
“Ten years ago, there was almost nothing for lung cancer,” said Giuseppe Giaccone, an oncologist at Georgetown Lombardi Comprehensive Cancer Center and an investigator in the trial. “Then we got targeted therapies for small subsets of patients, and now we have this immunotherapy for a larger group.” He thinks that scientists “are just at the beginning with immunotherapy,” with more gains to follow as they learn how to better use it.
Ruzanna Hovanesian, an 81-year-old resident of Glendale, California, is enthusiastic about her treatment. A smoker for 44 years who dropped the habit two decades ago, she was diagnosed in July 2013 with advanced lung cancer. She never received chemo, instead enrolling in an early Keytruda trial that caused only minor side effects, she wrote in an email. Today, she said, “I feel very good.”
“What is most exciting is that this is not an anecdotal response,” said Edward Garon, an oncologist at the University of California at Los Angeles who treated Hovanesian and was an investigator in the Keytruda trial. “Although patients with results like this are a minority, they are still a significant segment of the patients treated.”
In many ways, what’s happening in lung cancer is emblematic of the overall field of oncology. Immunotherapy has been approved for several types of cancer, but its ultimate power is not yet clear. In some cancers, like the pancreatic form, it has had little effect. And even in cancers in which it does work, usually only a minority of individuals are helped, and it can cause side effects.