Actionable Mutations Present in Younger Patients With Lung Cancer

Barbara Gitlitz, MD

The majority of patients under the age of 40 who have lung cancer had tumors with mutations that can be targeted with existing therapies, according to a preliminary analysis of data from an ongoing study recently reported at this year’s World Conference on Lung Cancer (WCLC).

In the study that analyzed the tumor genomics in younger patients, 60 of the first 68 patients enrolled had adenocarcinoma. In patients with metastatic adenocarcinoma, who represented the majority of participants, three-fourths of the tumors had actionable mutations.

Preliminary findings exceeded statistically derived expectations for discovery of actionable mutations in younger patients who have metastatic adenocarcinoma, reported Barbara Gitlitz, MD, at the conference.

“We had a 33-year-old male who had a 7-month partial response and at progression, he had increased copy number, which is consistent with emergence of resistance inEGFRmutations, and the transformed mutations were also amenable to tyrosine kinase inhibition,” stated Gitlitz, an associate professor of Clinical Medicine at the University of Southern California in Los Angeles.

The results came from the ongoing Genomics of Young Lung Cancer study, which aims to determine the genomic profile of lung cancers that occur in younger patients. Studies reported at the WCLC suggested that younger patients account for a proportion of lung cancer incidence that continues to increase. The tumor genomics of that specific subgroup of patients has been given little attention, due to the fact that younger patients historically constituted a relatively modest fraction of the total lung cancer burden.

The study, which was initiated a year ago, is enrolling patients at centers in the United States and Europe. Additionally, individuals can register for the study online and receive information about the nearest location that can provide the necessary genomic analysis.

Gitlitz said 30 of the first 68 study participants enrolled online and helped to expand the number of participating centers in the process. Information about online enrollment is available at https:www.openmednet.org/site/alcmi-goyl.

The study’s primary objective was originally to obtain multicenter, prospective genomic data for primary lung cancer in 60 patients below the age of 40, an accrual goal which has already been exceeded. With that information, investigators hope to gain insight into lung cancer biology associated with younger patients, as well as facilitate identification of new genome-defined subtypes of lung cancer, expand and speed access to targeted therapies for lung cancer, and provide data that can form the basis for future studies of lung cancer risk and associated genetics.

Investigators in the study have identified seven genomic alterations of interest:EGFR,KRAS,HER2,BRAF,ALK,ROS1, andRET. The focus on those mutations was decided on the basis of data from the Lung Cancer Mutation Consortium, an initiative of 16 major US cancer centers that contribute tumor-genomic information obtained from lung cancer patients treated at the centers.

“We felt that our enriched subtype would show an increase in targetable alterations from 35% to 50% and subsequent increase in use of targeted therapy,” stated Gitlitz.

The data for the 68 patients enrolled thus far showed a median age at lung cancer diagnosis of 35 (range, 16-39), including 33 men and 35 women. Consistent with the literature on lung cancer, 88% (n = 60) of patients had adenocarcinoma, 10% (n = 7) had squamous-cell tumors, and one patient had small-cell lung cancer.

Gitlitz reported that 54 (79%) of the 68 patients had stage IV disease at diagnosis and the remaining patients had stages I-III. In the subset of patients with adenocarcinoma, 50 (74%) had stage IV disease at diagnosis.

Focusing on the 50 patients with stage IV adenocarcinoma, Gitlitz stated that genomic analysis showed that the driver mutation involvedALKin 22 (44%) patients, EGFRin 13 (26%), and ROS1in three (6%) patients.

In five cases, data were insufficient to determine the driver mutation. The remaining seven (14%) patients had other types of mutations:EGFR-RAD1,EGFR Dup,HER2,ATM,BRCA2,p53/PTEN, andp53. Only one of these mutations occurred in a woman, which suggests a difference between men and women, as 90% of the women in the stage IV adenocarcinoma subgroup had tumors withALK,EGFR, orROS1mutations.

Gitlitz BJ. The Genomics of Young Lung Cancer Study. Presented at: 16th World Conference on Lung Cancer; September 6-9, 2015; Denver, CO. Abstract 3632.

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