Treatment for lung cancer has traditionally been based on the tumor’s histology (what it looks like under the microscope), but a new approach of basing treatment on genomic features has now been shown to result in better survival.
Results from the Lung Cancer Mutation Consortium (LCMC) show that patients who received genotype-directed therapy lived more than a year longer than those who did not.
The evidence that using targeted agents improves survival in lung cancer has been very difficult to show in clinical trials, but the current study shows that such an approach is not only feasible but successful. In fact, the study heralds a new era in the management of patients with a variety of cancers, Dr. Boris Pasche (Wake Forest University, USA) explains.
The Study: The LCMC, a collaborative, 14-center study led by Mark G. Kris, MD, from Memorial Sloan-Kettering Cancer Center, in New York City, tested tumors from 1007 patients with metastatic (spread to distant sites; incurable) lung adenocarcinomas for the presence 10 oncogenic driver mutations and then used the results to select agents that would target the drivers. The study was conducted from 2009 through 2012, and the patients’ tumors were tested for at least 1 gene, with full genotyping (testing for 10 genes) performed in 733 patients. For the other patients, the primary reason for the inability to test for all 10 genes was insufficient tissue.
The Small Print: An cancer driver was found in 466 (64%) of the patients who underwent full genotyping. So-called KRAS mutations were the most frequent, found in 182 (25%), followed by sensitizing EGFR in 122 (17%) and ALK rearrangements in 57 (8%). Less common drivers were other EGFR in 29 (4%), 2 or more genes in 24 (3%); ERBB2 (formerly HER2) in 19 (3%); BRAF in 16 (2%), PIK3CA in 6 (<1%), MET amplification in 5 (<1%), NRAS in 5 (<1%), and MEK1 in 1 (<1%). These results were then used to guide the choice of targeted therapy.
The Evidence: Overall, among 938 patients with adequate data, the median survival was 2.7 years. For patients with an oncogenic driver treated with targeted therapy, the median survival was 3.5 years, for patients with an oncogenic driver who were not treated with targeted therapy, the median survival was 2.4 years, and for patients with no driver identified, the median survival was 2.1 years (P < .001).
Among the different drivers that were identified, the longest survival was seen in patients with ALK-positive tumors (4.3 years).
“We are at the point now where we may be able to offer patients other treatments by studying the genomic features of their cancer. Until recently, we could not afford to do it because it cost about a million dollars for one genome. Now it’s as low as $900 to do the genome of a tumor, and it’s likely that will become even cheaper. And with better software, we would also be able to assess the unique features of that tumor vs other tumors and vs the normal DNA of that patient, and this is really the major change,” he said.
I’m Dr. Michael Hunter, and welcome to the future.
The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.
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Reference: JAMA. 2014;311:1988-206; Medscape 20 May 2014