Personalized Medicine & Lung Cancer
By MELANIE KILGORE-HILL
Lung cancer is no longer an automatic death sentence thanks in part to work being done in Nashville, including studies at Sarah Cannon Research Institute, the research arm of HCA's Cancer Institute - Sarah Cannon. Daily discoveries are shedding light on the common diagnosis that is still responsible for claiming more than 155,000 lives annually.
According to the American Cancer Society, approximately 222,000 cases of lung cancer are diagnosed annually, and it represents the No. 1 cause of cancer deaths in both men and women.
Two out of three people diagnosed with lung cancer are 65 or older, and black men are about 20 percent more likely to develop lung cancer than white men. However, the rate is about 10 percent lower in black women than in white women.
Early detection is key to survival, said oncologist Melissa Johnson, MD, associate director of Lung Cancer Research at Sarah Cannon Research Institute. An associate with Tennessee Oncology, Johnson is responsible for supporting the growth of Sarah Cannon's Phase 2/3 Lung Program clinical trial portfolio, while also furthering the development of early phase compounds for thoracic malignancies in the Drug Development Unit.
Melissa Johnson, MD
"We believe clinical trials are the way we'll move the bar forward in terms of developing effective therapies," Johnson said. "We don't have enough (FDA-approved) therapies that are standard of care."
Sarah Cannon offers more than 500 clinical trials per year including around 50 that enroll patients with lung cancer. And while trials might seem like a last ditch effort to some, Johnson said they're anything but. "The trials we offer add something extra to the standard of care, so a patient might be receiving a standard therapy in addition to a new drug or a combination of drugs that have already been approved individually but are now being investigated together," she said. "Patients don't need to be concerned they'll be randomly assigned to a placebo alone."
Personalized medicine is offering the most hope in the treatment of lung cancer. At Sarah Cannon, each patient's tumor and blood are continually examined to learn how a cancer might be evolving based on treatment. This helps physicians identify the best course of treatment, and change course when necessary.
"With all cancers, but with lung cancer in particular, we're learning more and more about how to personalize therapy for a particular patient's cancer by examining the molecular changes which make up each tumor," Johnson explained. "That genomic profiling is critical to finding the best therapy."
Over the past five years, researchers have grasped a clearer understanding of the role of genetics as the underlying cause of cancer development. "As each cancer evolves differently, we need to investigate different types of drugs, be it drugs that rev up the immune system or target particular proteins found in tumor tissue," Johnson said. "Knowing which genes are activated within a tumor gives us much more information about how to effectively target that cancer. A personalized approach is so important these days - not just scientifically but also as we try to assign personalized care of each of our patients, who all have different needs and are trying to cope with their diagnosis."
For today's lung cancer patients, diagnosis is just the beginning of a very long journey. At Sarah Cannon, nurse navigators are assigned to every patient and help to arrange care, schedule appointments, and navigate across the cancer continuum.
"As cancer care has become more personalized, it's also become more complex and sub-specialized, and navigators help patients understand the process and feel more engaged," Johnson said.
Sarah Cannon has a large research and care network across the U.S. and UK. That network supports the 85 percent of oncology patients who receive treatments in the community they call home. "Our mission is to bring cutting-edge therapies to patients in communities in which they live so they have access to the leading treatments, as well as first-rate care, available at a large university," Johnson said. "It's very different from most academic models and we're very proud of that."
It's no surprise that nearly 90 percent of lung cancer diagnoses are in current or former smokers. But it's that remaining 10-15 percent of lung cancer patients who have never smoked a cigarette that initially peaked Johnson's interest in the field.
"There's a lot to say about tobacco-related risk factors associated with lung cancer development, but the whole reason I'm a lung cancer doctor is because I was intrigued by the fact that never smokers get lung cancer every day," she said. "I wanted to study that and help find effective therapies for all patients diagnosed with this illness."
Scientists are learning that these "never smokers" often have treatable mutations in their tumors triggered by a genetic predisposition. "We went from knowing about one genetic mutation to several in the past few years, and with every year we identify another small subset in a rather large population that can be targeted with molecular inhibitors. This is why clinical trials investigating targeted inhibitors are so important," Johnson said.
These mutations only exist in cancer cells themselves and can effectively be turned off through targeted therapies while preserving healthy cells. "We don't know what triggers mutation in healthy young people who never smoked, but we do know now to look for those mutations and how to treat them," Johnson continued.
Currently, there are at least seven FDA-approved targeted inhibitors, with other agents expected to win regulatory approval within the next year. Over the past few years, Johnson said there's been increasing recognition that all lung cancer patients need to be tested for genetic mutations up front, as targeted inhibitors can prove more promising than chemo. In fact, 30 percent of lung cancer patients now receive targeted inhibitor therapy without chemotherapy.
Many other lung cancer patients also have options other than chemo thanks to immunotherapy, which is proving especially successful in former smokers. That's because those tumors tend to be more inflamed - a necessary attribute that makes the immunotherapy able to work. Using molecular markers, researchers are now trying to determine the genetic underpinning for patients who will respond early with immunotherapy. The science is so promising that Sarah Cannon treated 500 lung cancer patients with immunotherapy trials in 2016 alone.
Early diagnosis is the biggest challenge for patients, and the only test for lung cancer is the CT scan. Unfortunately, never smokers and smokers alike often don't receive scans until long after symptoms begin.
"We are still working out who to screen for lung cancer with a chest CT and when to do it," Johnson said. "Its hard to know -- particularly for never-smokers - when to look beyond a chest X-ray."
She encouraged patients and providers to know that with so many new and effective treatment options, there has never been a better time to start making this diagnosis earlier. Today's therapies can offer patients a level of confidence that didn't exist 20 years ago.
"So much has evolved in this field. There's a lot to be hopeful for," Johnson said. "New therapies are well tolerated and can extend life and improve quality. There's a lot of opportunity, and there's nothing to be lost and lots to be gained for the early diagnosis of lung cancer."