When testing of lung cancer tumors identifies certain genetic alterations, drugs specifically targeting those genetic “events” lengthen patients’ lives, say researchers.
From 2009 through 2012, patients being treated for lung adenocarcinomas (the most common type of lung cancer) at 14 treatment centers in the Lung Cancer Mutation Consortium underwent genetic testing. Those patients whose genomics data identified oncogenic drivers (abnormalities responsible for cancers) then received drug treatment specifically aimed at those drivers.
Mark G. Kris, M.D., of Memorial Sloan Kettering Cancer Center in New York, and colleagues examined the frequency of oncogenic drivers in these patients, and the proportion of patients in whom this data was used to select treatments targeting the identified drivers, along with overall survival. Their findings, which appear in JAMA, show that patients with one or more oncogenic drivers and treatment with targeted agents had a median survival of 3.5 years—compared with 2.4 years for those patients with a driver and no targeted therapy, and 2.1 years for those patients with no driver identified.
How Targeted Therapy Works
“The idea behind this is that if you understand what sort of genetic events make a person’s cancer [be] a cancer, you can then match treatments to specifically counteract those genetic events,” Kris explained to Healthline. “And because you’re going after those specific genetic events, which the cancer cells depend on for their life, you more effectively kill them.”
Patients for whom no genetic event can be found or identified receive chemotherapy directed against growing cells. “Chemo does work,” Kris said, “but it’s not as precise. Plus, normal growing cells are attacked as well—hence the loss of hair and other side effects.”
The study’s results, he added, have encouraged the researchers and given them more confidence that their approach—finding genetic changes and then going after them—is the right one.
Since the program began, the research team has identified additional genetic changes, according to Kris. “When we started, there was really only one target and one drug. Now there are a dozen different targets, plus drugs available to be used against those targets.”
Clinical Trials Suggested
Although these targeted treatments do not cure lung cancer, Kris stressed that they do more than simply lengthen lives: “The decency of patients’ lives is better. Also, just being able to take a pill, as opposed to having to come to a hospital every couple weeks and get an intravenous treatment, is so much less disruptive.”
In a press statement, JAMA cautioned that randomized clinical trials, the gold standard in medical research, “are required to determine if this treatment strategy improves survival.”
But such trials—where some qualified people get the treatment, and some people don’t—are problematic in this patient population, according to Kris.
He explained, “I can tell you, based on the tests, that I can virtually guarantee you’re going to have a (tumor) shrinkage; whereas giving you intravenous chemotherapy, I can’t make that guarantee. Which treatment are you going to accept, as a human being?”
Kris believes the whole issue of what is required for meeting the standard of medical evidence is changing, noting that two cancer drugs (crizotinib and ceritinib) recently received approval based on information from fewer than 300 patients and without randomized trials.
“Because the degree of benefit and the tolerability of these drugs so clearly supersedes what you see with the standard intravenous chemotherapy, our regulatory bodies and the consensus groups are willing to accept these as new kinds of treatment. So, yes, to prove with absolute scientific rigor, you need a randomized trial, where some people get the treatment and some don’t—but I think it’s very unlikely to happen because of the nature of these new treatments,” said Kris.
Looking for New Targets, Better Drugs
In a JAMA editorial accompanying the study results, Boris Pasche, M.D., Ph.D., of Wake Forest Baptist Medical Center, wrote, “much remains to be done.” Pasche told Healthline, “Targeted therapies work, but they are not the panacea. Patients live longer, but they are not permanently in remission, so clearly we need to have better drugs. For most patients with an actionable driver, we do not have a drug that we can readily prescribe.”
Pasche does see progress. “This study clearly shows the benefit of doing upfront genomic testing, where new patients with a new diagnosis of lung cancer would be tested for multiple potential drivers. And if we could have a sizable fraction of these patients in trials that will test the efficacy and safety of drugs that target these actionable drivers, we will make rapid progress in the field.”
Kris told Healthline that his group is moving on to the next phase. “We are looking for new targets, and we are trying to find more drugs and better drugs. That’s our push, rather than to do a trial,” he said.
Pointing out that both of the drugs used in their study and the genetic testing are available anywhere, Kris said, “Everybody with cancer has the biopsy that always goes to the pathology department, and the pathologists can decide whether they would do the test themselves or get another laboratory to do it for them. These tests that we’re talking about are available to every person in America who has a biopsy for lung cancer. It’s not research.”