Screening for mutations helps doctors choose targeted therapies that could increase survival, researchers say
By Amy Norton
TUESDAY, May 20, 2014 (HealthDay News) -- Testing lung cancer patients' tumors for various gene mutations may help doctors choose the best treatment, and possibly extend people's lives, a new study suggests.
Experts said the findings, reported in the May 21 Journal of the American Medical Association, are part of an ongoing "sea change" in treating lung cancer -- the biggest cancer killer in the United States.
The goal is to make it routine to test patients' tumors for a wide range of gene mutations, and then -- whenever possible -- treat them with newer drugs that specifically target that genetic flaw.
"Ten years ago, we were giving everyone 'chemotherapy X,'" said Dr. Mark Kris, an oncologist at Memorial Sloan Kettering Cancer Center in New York City, who led the new study.
But newer drugs and other substances known collectively as "targeted therapy" are different from traditional chemotherapy. They zero in on molecular processes that allow cancer cells to grow and spread, and may work better than chemo while causing fewer side effects.
They also come in pill form, Kris said, so people don't have to travel for treatment.
The new study included just over 1,000 patients with advanced lung cancer, from 14 medical centers across the United States.
Of those patients, about one-third were tested for at least one gene mutation, while 733 were able to have their tumors analyzed for 10 different mutations in a single test. The mutations are all known to drive the growth and spread of tumors. More importantly, there are targeted therapies available for all -- either already on the market, or in the form of experimental treatments being tested in clinical trials.
Kris' team found that nearly two-thirds of those 733 patients had at least one of the gene alterations. In the end, 44 percent of them received a targeted therapy. And overall, those patients lived longer -- typically surviving for 3.5 years, versus 2.4 years for patients who had a gene mutation but did not receive targeted therapy.
The findings offer a "proof of principle" that lung cancer patients can be tested for multiple gene mutations at once, and the information can guide treatment, said Dr. Boris Pasche, an oncologist at Wake Forest Baptist Medical Center, in Winston-Salem, N.C.
Like Kris, he said that is far different from the traditional approach of one-size-fits-all chemo. "We've made progress against this disease in recent years," said Pasche, who wrote an editorial published with the study. "We're moving toward much more targeted treatment."
Already, guidelines recommend that lung cancer patients be tested for mutations in two genes, known as EGFR and ALK. In a minority of patients, those mutations help fuel the cancer, and there are several drugs on the market that target them -- such as erlotinib (Tarceva), afatinib (Gilotrif) and crizotinib (Xalkori). Additional drugs are under development.
In the United States, the majority of lung cancer patients are now tested for those "big two" genes, Kris said.
But this study suggests that simultaneously testing for a range of mutations can help get more patients the "right therapy, right off the bat," Pasche said.
The genes Kris' team analyzed included the EGFR and ALK genes, as well as eight others -- like the HER2 gene that is best known for its link to some breast cancers, but can also be mutated in several other cancers.
Study patients who tested positive for any of those mutations were either offered a targeted drug that was already approved for cancer (even if not lung cancer, specifically), or could enter a clinical trial testing an experimental therapy.
In the end, only 28 percent of the whole study group and 44 percent of those who got the 10-gene test ended up receiving a targeted therapy.
It's not clear why, Kris said. But, he noted, when the study started in 2009, there were fewer approved drugs, and many patients may not have wanted to enter a clinical trial.
Pasche said the findings "pave the way" for further studies testing the value of multi-gene testing, in lung and other cancers.
But in fact, such testing is already available -- not only at the 14 centers in this study, but others as well, Kris said.
Pasche suggested that lung cancer patients who've already tested negative for the EGFR and ALK mutations should ask their doctor if testing their tumor tissue for other genes is an option. Insurance may cover it, according to Pasche.
The American Cancer Society offers this advice on genetic testing: "Genetic testing is complicated, and it can cost a lot. Some tests cost more than others, but the final bill can be thousands of dollars. Be sure you have an idea of how much it will cost you before you have testing done."
The existing targeted therapies for lung cancer are not a cure, they're very expensive, and they can have side effects -- like skin rash and diarrhea. But, Kris said, they also avoid the more serious side effects of chemo, like debilitating nerve damage.
The current study was funded by the U.S. National Cancer Institute. Kris and his co-researchers have financial ties to various companies developing targeted therapies.
The American Cancer Society has more on targeted therapies for lung cancer.
SOURCES: Mark Kris, M.D., Ruane chair, thoracic oncology, Memorial Sloan Kettering Cancer Center, New York City; Boris Pasche, M.D., Ph.D., director, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, N.C.; May 21, 2014, Journal of the American Medical Association
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