Most young patients with lung cancer harbor targetable mutations

Issue: October 10, 2015

Patients with lung cancer aged younger than 40 years appeared likely to harbor mutations that would lead to more effective treatments, according to study results presented at the World Conference on Lung Cancer.

Because lung cancer is heterogeneous, Barbara J. Gitlitz, MD, associate professor of clinical medicine at University of Southern California Keck School of Medicine in Los Angeles, and colleagues hypothesized young age at the time of lung cancer diagnosis may be a clinical characteristic associated with likelihood to harbor a targetable genomic alteration.

“We aim to demonstrate that the prevalence of targetable genomic alterations will be greater in our population compared to the Lung Cancer Mutational Consortium and have powered our study to show an increase from 35% to 50%, and an improvement in use of targeted therapy from 22% to 40%,” Gitlitz said in a press release.

Researchers noted the accrual method for the study — which opened in July 2014 and is still ongoing — is unique in that it is available online and utilizes social media. An online study website allows for consent so patients can participate from anywhere in the world and can discuss progress and outcomes through social media. Forty-four percent of the initial patients enrolled signed up online.

Eligible patients are aged younger than 40 years and have been diagnosed with bronchogenic lung cancer.

Based on data from the Lung Cancer Mutational Consortium, researchers focused on seven genomic alterations: EGFR, KRAS, HER-2, BRAF, ALK, ROS1 and RET.

Gitlitz presented data from the first 68 patients to enroll onto the study. The median age at time of diagnosis was 35 years (range, 16-39) and 35 of the patients were female. A majority of the patients (88.2%) had adenocarcinoma. Squamous cell tumors were found in 10.3% of the patients and one patient had small cell lung cancer.

Most of the patients presented with stage IV adenocarcinoma (79%).

Overall, a large portion of the population with stage IV disease had ALK mutations (44%). The second most prevalent gene alteration was EGFR (26%) and third was ROS1 (6%). These data combined suggest 76% of the population harbored an actionable mutation for which targeted therapies exist.

Fourteen percent of patients harbored another alteration, such as EGFR-RAD1, EGFR duplication, HER-2, ATM, BRCA2, p53/PTEN and p53.

“We came up with some interesting genetic alterations in an additional 14% of people,” Gitlitz said during a press conference. “Only one of them was attributed to a female, so there may be a different genetic spectrum of females to males. Almost 90% of the females that came into our study had ALK, EGFR or ROS1 mutations.”

Gitlitz added that one of these mutations was a novel finding, and that international participation in this study may help to streamline the best targeted therapies to target this mutation.

“The EGFR-RAD1 fusion is being studied now to see if it is an actionable EGFR mutation,” Gitlitz said. “The EGFR kinase domain duplication that was discovered was published (Gallant JN et al, Cancer Discov. 2015;doi:10.1158/2159-8290.CD-15-0654) and it is an actionable mutation.

“A 33-year-old man who had a 7-month partial response with afatinib [Gilotrif, Boehringer Ingelheim], at progression, had an increased copy number, which is the typical route of emergence of resistance in EGFR mutations; and so this transformed to express this mutation, which was also amenable to tyrosine kinase inhibition,” Gitlitz said. “A new, actionable mutation has been discovered by looking at young people with emergent lung cancer.” – by Anthony SanFilippo

Reference:

Gitlitz BJ, et al. Genomics of young lung cancer study. Presented at: 16th World Conference on Lung Cancer; Sept. 6-9, 2015; Denver, Colorado.

Disclosure: The researchers report no relevant financial disclosures.