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Fourteen American centres tested a thousand lung adenocarcinomas for ten genes at once and found a driver in about two thirds. The patients whose treatment was chosen to match their driver lived about a year longer.
From 2009 to 2012, 14 sites enrolled patients with metastatic lung adenocarcinoma and tested their tumours for ten oncogenic drivers. Tumours from 1,007 patients were tested for at least one gene and 733 for all ten. An oncogenic driver was found in 466 of 733, 64%. Among those 733 tumours, 182 had KRAS (25%), 122 sensitising EGFR (17%), 57 ALK rearrangement (8%), 29 other EGFR (4%), 24 two or more genes (3%), 19 ERBB2 (3%), 16 BRAF (2%), 6 PIK3CA, 5 MET amplification, 5 NRAS and 1 MEK1, with no AKT1. Results were used to select a targeted therapy or trial in 275 of 1,007 patients, 28%. Median survival was 3.5 years for the 260 patients with an oncogenic driver who received genotype-directed therapy against 2.4 years for the 318 with a driver who did not, with a propensity-adjusted hazard ratio of 0.69.
It is the study that made multiplex testing standard practice in lung adenocarcinoma, by showing both that most tumours have a driver and that finding it changes what patients receive.
Shares Non-small cell lung cancer (KEGG map), Driver mutation, Next-generation sequencing (NGS), MET.
Shares ALK fusion (ALK-positive), Cytogenetics and FISH, Non-small cell lung cancer (KEGG map), Next-generation sequencing (NGS).
Shares Next-generation sequencing (NGS), MET, ALK, Receptor tyrosine kinase activation.
Shares Next-generation sequencing (NGS), MET, ALK, Receptor tyrosine kinase activation.
Shares HER2 (ERBB2) activating mutation, Driver mutation, MET, ALK.
Shares NRAS, Wild-type (WT), Next-generation sequencing (NGS), BRAF.
Shares ALK fusion (ALK-positive), Wild-type (WT), MET, ALK.