Video courtesy of the Journal of the American Medical Association.
Smarter cancer therapy. For more than a decade, as research has provided more and more data about the genetic underpinnings of various cancers, this has been the goal of investigators seeking to devise better treatments with fewer side effects. Rather than taking the approach of traditional cancer therapies, which attack all rapidly dividing cells, these new drugs target the specific genetic changes inside cancer cells.
Now a study from a multicenter consortium co-led by Memorial Sloan Kettering has found that driver mutations — genetic changes that directly induce cells to become cancerous or spur their malignant behavior — can be found in about two-thirds of patients with advanced lung adenocarcinomas. Furthermore, survival was increased for patients who were given drugs matched to specific driver mutations.
“Since the discovery of the first gene linked to lung cancers in 2003, Memorial Sloan Kettering has made the testing of genetic mutations in lung tumor specimens our mission,” says Mark G. Kris, the William and Joy Ruane Chair in Thoracic Oncology and one of the leaders of the new study. “It’s been a priority to do this for every person with lung cancer treated here.”
In 64 percent of patients tested for all ten target genes, the investigators were able to uncover a genetic driver. The most common mutations were those in genes called KRAS, EGFR, and ALK. Of these patients, 28 percent were given a therapy designed to target the mutation driving their individual cancers. The average survival of patients receiving a targeted drug was extended more than a year, from 2.4 years to 3.5 years.
“This testing is all about information, giving your doctor the information that can assist him or her in making the best choice for you, and providing that personalization of care,” Dr. Kris says. “This study shows that you can get useful information this way, and that it ultimately leads to a targeted therapy in more than a quarter of cases.”
Memorial Sloan Kettering Leads the Way
“Lung cancers are the model for how to treat patients with targeted cancer therapies. We’ve been doing it since 2004,” Dr. Kris says. That year, Memorial Sloan Kettering’s Molecular Diagnostics Service, led by molecular pathologist Marc Ladanyi, developed a test — the first of its kind approved by the state of New York — to test our patients with lung cancers for the EGFR gene mutation. (Researchers here and at two institutions in Boston had discovered the mutation the previous year.)
Based on the EGFR test results, patients could be given the drug Iressa® (gefitinib) or Tarceva™ (erlotinib), both of which have been shown to target EGFR mutations.
Dr. Kris notes that Memorial Sloan Kettering’s testing capabilities have grown tremendously in the past decade. With its latest genetic testing assay, known as MSK-IMPACT, the institution can now simultaneously search across 341 cancer-related genes for mutations in every patient sample. Genomics researcher Michael Berger and Dr. Ladanyi led the development and clinical implementation of MSK-IMPACT.
There are already targeted therapies available for many of these 341 genetic changes, including drugs now in wide use and compounds in various stages of clinical trials.
The next step for the LCMC is to routinely identify more targets, such as RET, another lung cancer target with a matched therapy that is under study by Memorial Sloan Kettering investigators. Next-generation inhibitors of ALK and EGFR are being studied as well.
On a broader scale, Memorial Sloan Kettering physicians and scientists will continue to test all patients with advanced cancers to look for driver mutations, and to match those patients with the treatments that are most likely to provide a benefit.
“Being able to do this kind of genetic testing was a vision in 2003” shortly after the Human Genome Project was completed, Dr. Kris concludes. “In 2014, it’s become a reality, and this study is just one example of how this information can help us make better treatment choices for all people with cancers.”
This study was funded by the National Cancer Institute under grant 1RC2CA148394-010.