03:50am Saturday 29 February 2020

Lung cancer found to be genetically different disease in young and older patients

Adrian Sacher, MD

In a study published online today by JAMA Oncology, investigators scanned the DNA of thousands of NSCLC tumor samples for abnormalities and found that younger patients were more apt to have genetic subtypes of the disease that can be treated with available targeted therapies.

“We discovered that tumor tissue in patients under age 50 was more likely to have alterations in any of five genes that we studied, for which targeted therapies already exist or are in clinical development,” says the study’s lead author, Adrian Sacher, MD, of Dana-Farber and Brigham and Women’s Hospital. “We also found differences in the biology and behavior of NSCLC in younger and older patients.”

Those differences became apparent when investigators compared survival statistics for the youngest and oldest patients in the study. Even though “targetable” abnormalities were more common in young patients’ tumors, these patients’ survival times were shorter than expected when the beneficial effect of targeted therapy was taken into account. This suggests that NSCLC is inherently more aggressive in younger patients, researchers say: Even though targeted therapy can lengthen patients’ survival, that gain is counterbalanced by the more virulent nature of the disease in young patients.

The findings reinforce the need to test young patients’ NSCLC tissue for the full array of genetic aberrations that can be therapeutically targeted, whether by already-approved drugs or by newer agents being tested in clinical trials, the study authors state.

NSCLC is the most common form of lung cancer, accounting for about 87 percent of all lung cancer cases. The median age at diagnosis is 70, with less than 5 percent of patients diagnosed prior to age 50. Although younger people constitute a relatively small portion of all NSCLC patients, their overall number is quite large. More than 192,000 new cases of NSCLC are diagnosed in the U.S. every year, according to American Cancer Society figures. Five percent of that figure – corresponding to the number of patients under 50 – is 9,600.

Previous research has suggested that certain genetic abnormalities are associated with NSCLC in young patients, but no previous study had done a broad survey comparing the genetic features of younger and older patients’ tumors.

For the new paper, Sacher and his colleagues scanned NSCLC tissue from 2,237 patients, looking for abnormalities in eight genes that can be targeted by existing drugs or agents under development. They found that alterations in five targetable genes – EGFR, ALK, HER2, ROS1, and BRAF V600E – were more frequent in younger patients. Patients diagnosed at age 50 or younger were 59 percent more likely than older patients to harbor one of these mutations in their tumors.

“Our findings suggest that younger patients with NSCLC represent a genetically unique subgroup,” Sacher says. “This has implications for how the disease is treated. Because younger patients are more likely to have a targetable form of the disease, it’s absolutely vital that their tumor tissue undergo comprehensive genetic testing including all targetable genomic alterations. This will ensure that they reap the full benefit of the targeted therapies that are now coming on line for NSCLC.”

Spurred by the results of the study, researchers are offering advanced genetic sequencing to all patients under the age of 40 who are diagnosed with lung cancer. The testing, performed with the FoundationOne genomic profiling system, aims to identify genomic targets in patients’ tumors and help patients gain access to targeted therapies that may benefit them. Young lung cancer patients can participate remotely via a study website, www.openmednet.org/site/alcmi-goyl.

This international study is led by Geoffrey Oxnard, MD, of Dana-Farber and Brigham and Women’s, the senior author of the JAMA Oncology study, and by Barbara Gitlitz, MD, of the University of Southern California, and coordinated by the Addario Lung Cancer Medical Institute (ALCMI).

The co-authors of the JAMA Oncology study are Suzanne Dahlberg, PhD, of Dana-Farber and the Harvard T.H. Chan School of Public Health; Jennifer Heng and Stacy March of Dana-Farber; and Pasi Jänne, MD, PhD, of Dana-Farber and Brigham and Women’s.

Support for the study was provided by the National Institutes of Health (grants R01CA114465 and P50CA090578), the Conquer Cancer Foundation of the American Society of Clinical Oncology, the Bonnie J. Addario Lung Cancer Foundation, the Canadian Institutes of Health Research, the Canadian Association of Medical Oncologists, the Gallup Research Fund, and the Kaplan Research Fund.

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