Related Experiment Video
Updated: Feb 28, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs
Mark G Kris1, Bruce E Johnson2, Lynne D Berry3
1Memorial Sloan Kettering Cancer Center, New York, New York.
Importance:
Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials.
Objectives:
To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival.
Design, Setting, And Participants:
From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival.
Interventions:
Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies.
Main Outcomes And Measures:
Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival.
Results:
From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006).
Conclusions And Relevance:
Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival.
Trial Registration:
clinicaltrials.gov Identifier: NCT01014286.
Insights
Multiplexed testing identified actionable oncogenic drivers in 64% of lung adenocarcinoma patients. Genotype-directed therapy was associated with improved survival, though further randomized trials are needed.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Targeting oncogenic drivers has significantly improved lung adenocarcinoma treatment.
- The Lung Cancer Mutation Consortium aimed to identify these drivers for personalized therapy.
- Multiplexed assays were developed to test for multiple genomic alterations simultaneously.
Purpose of the Study:
- To determine the frequency of oncogenic drivers in lung adenocarcinomas.
- To assess the utility of genotype-directed therapy selection.
- To measure survival outcomes in patients receiving targeted treatments.
Main Methods:
- Tumor samples from 1007 patients with metastatic lung adenocarcinoma were tested for 10 key oncogenic drivers.
- Genotyping results guided the selection of targeted therapies or clinical trial enrollment.
- Survival data was collected and analyzed for patients with and without genotype-directed therapy.
Main Results:
- An actionable oncogenic driver was identified in 64% of 733 fully genotyped tumors.
- KRAS mutations (25%) and EGFR mutations (17%) were the most frequent drivers.
- Patients receiving genotype-directed therapy demonstrated significantly longer median survival compared to those who did not.
Conclusions:
- Multiplexed molecular profiling is effective in identifying actionable drivers in lung adenocarcinoma.
- Genotype-directed therapy selection aided clinical decision-making.
- While promising, randomized controlled trials are necessary to definitively confirm improved survival with targeted therapies.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...