Inside the Lab Industry: Will Lab Sector Develop a Test for the Deadliest Form of Lung Cancer?

Molecular testing in combination with the practice of oncology has made great strides in the past decades. There are assays for tumor evaluation and even those that predict risk for some of the most common forms of the disease. In many ways, these tests have revolutionized the way oncology care is delivered. Based on test results, doses of chemotherapy have been adjusted accordingly or abandoned altogether for other treatments. The prophylactic mastectomy, for example, is a direct result of the BRCA test. Celebrities such as Angelina Jolie have raised the awareness of such testing by undergoing a preventive operation herself. But there remains a conspicuous absence in oncology-related testing for small-cell lung cancer. Lung cancer is the deadliest form of the disease both in the United States and the rest of the world. And the small-cell form is perhaps the deadliest cancer of all. The five-year survival rate of small-cell lung cancer is just 31 percent if detected in the earliest stage of the disease—less than a third the rate for breast cancer. Survival rates are less than 20 percent for stage 2, and a decidedly bleak 2 percent for those in the late stage of the disease. According to the American Cancer Society, the overall five-year survival rate for all small-cell lung cancer patients is a mere 7 percent. And like most lung cancers, the small-cell form of the disease is rarely detected in the earliest stages because patients are usually asymptomatic at its onset. It also spreads much more rapidly than its non-small-cell counterpart. Despite the fact that only about 15 percent of lung cancer cases diagnosed are of the small-cell variety, 30,000 Americans still die each year die from that form of the disease. That’s well over 20 percent of the total lung cancer fatalities, an outsized proportion of all deaths given the prevalence of small-cell lung cancer. The National Cancer Institute (NCI) noted in a recent report to Congress that little progress has been made in battling the disease over the past three decades. “Avoidance of the use of tobacco is the only known way to prevent the disease; no screening method has proved effective . . . and life expectancy after diagnosis tends to be very short,” the report said. The typical treatment is chemotherapy and radiation therapy, with no guidance as to how a specific patient might respond—“the prevailing state-of-the-art from the early 1980s,” the report noted. Most patients also quickly develop resistance to chemotherapy. Despite the need for sharper diagnostic tools, none currently exist. “I am not aware of any current, commercially available molecular assays used to diagnose patients with small-cell lung cancer,” said Peter Francis, president of Clinical Laboratory Sales Training, a Maryland-based consulting firm. Little Infrastructure for Development Meanwhile, the infrastructure for developing a similar test for small-cell lung cancer is all but nonexistent. Most esoteric tests are based on prior genetic research and preservation of the relevant cell lines. “We don’t have proper modern systems to study the disease at all, no cell lines or animal models, and no patient samples,” said Guneet Walia, director of research and medical affairs at the Bonnie J. Addario Lung Cancer Foundation. Since surgery is useless for treating small-cell lung cancer patients, most tissue samples are from biopsies and are too small to perform extensive genetic research. The NCI report noted that this is hindering research on determining biomarkers for chemotherapy resistance. Partly as a result, the NCI has created a new framework for combating small-cell lung cancer, including improving the collection of small-cell lung cancer tissues, creating new tumor profiles for the disease as it progresses, and the investigation of “new diagnostic approaches for populations at high risk of developing small-cell lung cancer.” In other words, a predictive risk assay for the millions of Americans who smoke or are former smokers—the cohort with the greatest probability of developing the disease. The framework, which was announced last month, drew mostly praise from anti-cancer advocacy groups. “Our long sought effort to devise a national strategy to improve lung cancer’s survival rate has taken a concrete step forward,” said Lung Cancer Alliance President Laurie Fenton-Ambrose. But whether the laboratory sector develops any sort of diagnostic tools for small-cell lung cancer anytime soon remains to be seen. Not Much Available From Labs Why the laboratory sector hasn’t developed a specific test for small-cell lung cancer when it has developed esoteric assays is a matter for debate. The vast majority of cancer victims have the non-small-cell variety of the disease. As a result, much of the research and test development have been on that form of cancer. Pinpoint Genomics, a small lab in Northern California, developed a polymerase chain reaction test that determined whether patients with the non-small-cell variety were at high risk of having the disease progress to a late stage after undergoing surgery to remove the tumor, which is the typical intervention to treat the disease. That surgery is often performed for non-small-cell lung cancer patients means far more tissue has been available to conduct the research to develop lab tests. Pinpoint was acquired by Life Technologies, a division of Thermo Fisher Scientific, in 2012. Life Technologies markets the assay as Pervenio Lung RS. Life Technologies officials estimated that the market for a comprehensive molecular lung cancer assay would be as much as $120 million a year in the United States and $500 million worldwide. A company spokesperson did not respond to a query regarding the development of a predictive or diagnostic test for small-cell lung cancer. If there is a test developed in the near future, it may come from outside of the United States. Walia of the Addario Lung Cancer Foundation noted that most of the relevant research is currently being performed in Europe. Researchers in the Netherlands are working on developing avatars of lung cancer tumors, while researchers in the United Kingdom are focused on isolating circulating tumor cells. Such cells have been the basis for many esoteric molecular laboratory tests. “This has the obvious advantage of being noninvasive, since it is a blood test,” Francis said. Walia also noted that researchers may also be able to link levels of volatile organic compounds in a patient’s body to their risk for developing lung cancer. Such compounds have been used to determine the level of exposure an individual has had to tobacco smoke. “The scientific community is very aware of the fact that more needs to be done, and the NCI is putting more money into research,” Walia said, noting that the establishment of the framework for fighting non-small-cell lung cancer will soon spur more research—and perhaps an eventual molecular assay. “Time and research will tell,” Francis said. Takeaway: There may be a market for a molecular test for small-cell lung cancer, but no laboratory has yet to take advantage of the opportunity, and the economies of scale for supporting such a test remain uncertain.