The stigma of blame and futility around lung cancer

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The stigma of blame, plus a sense of futility among some physicians, can contribute to the under-treatment of patients with advanced lung cancer, writes The Washington Post. Now the groundbreaking immunotherapy drug Keytruda is bringing a sea change.

Lung cancer, which kills almost 160,000 Americans a year, is among the cruelest of foes. Most patients are diagnosed at an advanced stage and after punishing chemotherapy still have a bleak prognosis. More than half die within a year. The Washington Post reports that 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% 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 US alone – as many as one-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 report says the US Food and Drug Administration last month approved Keytruda as a first-line treatment for such cases, the first time that immunotherapy has been given the green light as an initial treatment for lung cancer.

The result: Most new patients will be tested for the protein, called PD-L1. If they have a high level on their cancer cells, they will 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 an oncologist at the Sidney Kimmel Comprehensive Cancer Centre 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.”

The report says it’s decidedly good news in a field in which gains are excruciatingly hard to come by and funding lags behind that of many other types of cancer. The National Institutes of Health estimated that it would spend $362m on lung cancer research in fiscal 2016, compared with almost $700m for breast cancer research. Yet lung cancer kills four times as many people annually.

And, the report says, 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 under-treatment 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 that 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 Centre 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 says that scientists “are just at the beginning with immunotherapy,” with more gains to follow as they learn how to better use it.

The report says 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, such as 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.

Yet among those patients who do respond, some have what doctors call “durable remissions,” extending life far beyond the few months that might otherwise have been expected. Because the treatments are so new, researchers say, it’s impossible to know how long such remissions will last. And the cost of such progress is high given Keytruda’s $150,000 annual price tag.

In the Keytruda study, 70% of the patients who were given the drug, also known as pembrolizumab, were alive at one year, compared with 54% of the chemo group, Brahmer said. The median for ¬progression-free survival – the period during which the disease did not get worse – a was 10.3 months in the Keytruda group compared with six months in the chemo group. The Keytruda group also experienced significantly fewer serious side effects.

Although the difference might not sound barrier-breaking, it is significant in the research world. An independent monitoring committee was so impressed that it took the unusual step of recommending that the trial be halted early to allow the chemo patients to switch to Keytruda.

The trial also underscored the increasing importance of biomarkers – in this case, PD-L – in helping physicians decide who is likely to benefit from the new treatments. The study was restricted to patients who had PD-L1 on at least 50% of their cancer cells. Almost half of those in the Keytruda group had significant tumor shrinkage, compared with 28% in the chemo group.

Researchers say such biomarkers, which indicate the features of particular tumors, could pave the way for “individualized immunotherapy.” PD-L1 binds to another protein called PD-1, which is located on T cells, a key part of the immune system. When that “handshake” occurs, it discourages the immune system from attacking the cancer.

The report says Keytruda, made by Merck, is the only immunotherapy drug approved for previously untreated patients with advanced lung cancer. Other immunotherapy medications are approved as second-line therapies.

Researchers say that smokers and ex-smokers seem to benefit more from immunotherapy than nonsmokers. That may be because their cells have many mutations caused by cigarettes, which may make it easier for the immune system, once boosted by a drug, to see and attack the cancer.

The Keytruda trial involved more than 300 people who had advanced non-small-cell lung cancer, the most common form of the disease, but didn’t have certain high-risk mutations.

The Washington Post report
Trial material


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