Therapy Matched to Oncogenic Drivers Improves Survival in Metastatic Lung Adenocarcionoma
Results from the Lung Cancer Mutation Consortium
Results from the Lung Cancer Mutation Consortium presented at the Presidential Symposium of the 15th World Conference on Lung Cancer (27 October-30 October 2013, Sydney, Australia) show that patients with lung adenocarcinoma with oncogenic drivers receiving a corresponding targeted agent, lived longer than similar patients who did not. An actionable driver was detected in 64% of tumours from patients with lung adenocarcinomas and more than one was present in 3%. Multiplexed testing aided physicians in choosing therapies and targeted trials in 28% of patients.
Detecting & targeting oncogenic drivers: transforming patient care
According to background of the study presented by Dr Mark Kris of the Memorial Sloan-Kettering Cancer Center in New York, USA, detecting and targeting the oncogenic drivers EGFR and ALK have transformed the care of patients with metastatic non-small cell lung cancer. The Lung Cancer Mutation Consortium was established to use multiplexed assays to test tumours for alterations in 10 genes and provide the results to clinicians to select treatments and clinical trials matched to the driver detected.
Fourteen Lung Cancer Mutation Consortium sites enrolled patients with metastatic lung adenocarcinomas and tested their tumours in CLIA (Clinical Laboratory Improvement Amendments) laboratories for activating mutations in 10 oncogenic driver genes.
Tumours were tested from 1,007 patients for at least one gene and 733 for all 10 genes. An oncogenic driver was found in 466 (64%) of fully-genotyped cases. Among these 733 tumours, drivers found were: KRAS 182 (25%), sensitising EGFR 122 (17%), ALK rearrangements 57 (8%), 'other' EGFR 29 (4%), two genes 24 (3%), HER2 19 (3%), BRAF 16 (2%), PIK3CA 6 (1%), MET amplification 5 (1%), NRAS 5 (1%), MEK1 1 (<1%), AKT1 (0).
For cases with any genotyping, researchers used results to select a targeted therapy or trial in 275 (28%). Among 938 patients with follow-up, the median survivals were 3.5 years for the 264 with an oncogenic driver treated with genotype-directed therapy, 2.4 years for the 318 with an oncogenic driver with no genotype-directed therapy, and 2.1 years for the 360 with no driver identified (p<0.0001).
The authors concluded that patients with lung cancers with oncogenic drivers receiving a corresponding targeted agent lived longer than similar patients who did not. An actionable driver was detected in 64% of tumours from patients with lung adenocarcinomas, and more than one was present in 3%.
Multiplexed testing aided physicians in choosing therapies and targeted trials in 28% of patients. This authors argue that paradigm for care and research will expand as genotyping becomes more efficient with next-generation platforms, additional drivers are identified (i.e.ROS1 and RET), and more targeted drugs become available in the pharmacy and through clinical trials.
The study was supported by HSS NIH NCI 1RC2CA148394-01 grant.
The trial registration number within Clinicaltrials.gov is NCT01014286.
The World Conference on Lung Cancer is the world’s largest meeting dedicated to lung cancer and other thoracic malignancies. The 2013 theme is 'Next-Generation Lung Cancer Care.'