Physicians have become increasingly aware that all lung cancers are not the same. Rather, different types contain specific genetic mutations that affect how they progress and respond to therapies.
At Memorial Sloan Kettering, lung cancer patients now routinely receive genomic testing of their tumors as a part of diagnosis and staging. For certain mutations, drugs already approved by the US Food and Drug Administration are available as treatments. For others, experimental treatments being tested in clinical trials may be the best option.
“We’ve made it a priority to do genomic tumor testing for every person with lung cancer treated here,” says MSK medical oncologist Gregory J. Riely. “We feel strongly that this type of information is essential for selecting the optimal treatment.”
MSK has led the way in this kind of tumor testing. Beginning in 2004, every MSK lung cancer patient’s tumor has been tested for a mutation in the EGFR gene, which is present in many patients with non-small cell lung cancer. Over the next decade, tests for additional mutations — found in KRAS, ALK, and other genes — have been added, as well as tests for additional mutations in squamous cell lung cancer. Patients with these specific mutations can be matched with available drugs to treat their cancer or research studies evaluating new drugs thought to target these mutations.
Research has shown that this approach is already transforming lung cancer care. A study published earlier this year, led partly by MSK medical oncologist Mark G. Kris, found that driver mutations — genetic changes that induce cells to become cancerous or spur their malignant behavior — can be found in about two-thirds of patients with advanced lung adenocarcinoma, a subtype of non-small cell lung cancer. Furthermore, survival was increased for patients given drugs matched to specific driver mutations.
Another Leap Forward
In 2014, MSK greatly enhanced its genomic analysis of lung tumors with the introduction of MSK-IMPACT™, a test that examines 341 cancer genes that have been shown to play a role in the development or behavior of tumors. They represent all “actionable targets” — genes that can either be targeted with drugs or provide clinically relevant information about the disease if they are altered.
MSK-IMPACT is based on next-generation sequencing, cutting-edge technology that allows cancer genomes to be profiled very quickly and with great sensitivity. For example, the test can tell if a gene has been mutated or deleted, or if there are additional copies of it.
Dr. Riely explains that MSK-IMPACT allows clinicians to look for alterations that, while less common than EGFR, KRAS, and ALK mutations, still have important implications for choosing treatments.
“The IMPACT test includes the complete range of mutations that we can target in patients with lung cancer, and it does it all in one fell swoop rather than requiring multiple tests,” he says. “Its range is so broad that we might find some mutations that are each present in only 1 to 3 percent of patients — but when you add them all together, it probably represents another 10 to 15 percent of our patients who have an option for a new targeted therapy that would not have been possible before.”
For example, a phase II clinical trial led by MSK medical oncologist Alexander Drilon has been testing a targeted therapy, cabozantinib, in lung cancer patients whose tumors contain a mutation in a gene called RET. After MSK-IMPACT testing showed that a significant percentage of lung cancer patients had increased activity in a gene called MET — known to promote cancer cell growth through the same biological pathway as RET and thus likely to make tumors sensitive to the drug — the trial was expanded to include these patients.
“As the mutation testing continues to be applied to a growing number of patients, we will know more about the frequency of rare mutations and will be spurred to develop new clinical trials for patients with those mutations,” Dr. Riely says.
Dr. Riely says MSK-IMPACT will be refined periodically as new actionable targets are discovered. Even those mutations that are not currently “targetable” with drugs nonetheless could soon provide important information — for example, how the cancer might behave, or which treatment, whether a targeted drug or a conventional treatment like chemotherapy or radiation, will be more effective.
In some cases, MSK-IMPACT could reveal targetable mutations that are rare in lung cancer but may occur in other cancer types. These patients may be eligible for treatment in a new type of clinical study called a basket trial, which focuses on specific gene changes and may enroll patients with many different types of cancer whose tumors carry similar mutations.
“We’ve made remarkable progress over the last decade in lung tumor analysis, from testing just one gene to several hundred all at once,” Dr. Riely says. “As more information is gathered, we expect a continued increase in the percentage of lung cancer patients who we can match with a clinical trial, and ultimately with approved new drugs.”
Learn more about the MSK-IMPACT test and how our scientists developed it.Back to top