Targeted therapy of advanced non-small-cell lung cancer (NSCLC) has changed the outcome of patients with specific gene alterations. In particular, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have improved the outcome of patients with EGFR-mutated lung adenocarcinoma (ADC). We analyzed the frequency of other potentially targetable driver alterations in a series of advanced EGFR-wild type (wt) NSCLC patients.
461 advanced EGFR-wt NSCLC patients enrolled from Area Vasta Romagna between January 2013 to December 2014 were included in the study. KRAS, BRAF, ERBB2, PIK3CA, NRAS, ALK, MAP2K1, RET and DDR2 mutations were analyzed by Myriapod®Lung Status kit (Diatech Pharmacogenetics) on Maldi-TOF Mass Spectrometry (MassARRAY® AGENA BIOSCIENCE). ERBB4 was evaluated by direct sequencing and EML4-ALK and ROS1 rearrangements were assessed by immunohistochemistry or fluorescence in situ hybridization.
217 (47%) patients showed at least one alteration. In particular, 71%, 6.5%, 2.7%, 1.8%, 1.4% and 1.4% patients had mutations in KRAS, BRAF, PIK3CA, NRAS, ERBB2 and MAP2K1 genes, respectively. Only one (0.5%) patient showed a mutation in ERBB4 gene. EML4-ALK and ROS1 rearrangements were observed in 10.6% and 4.1% patients, respectively. The clinical characteristics of mutated patients are reported in Table 1. Overlapping mutations were observed in 5 (2.3%) KRAS-mutated patients: one (20%) was mutated in PIK3CA, 3 (60%) showed an EML4-ALK translocation and one (20%) had a ROS1 rearrangement. One (0.5%) patient showed both BRAF and PIK3CA alterations. Correlation analyses between the different mutations and patient outcome are ongoing. Table.
|Gene||No. of mutated patients||Age||Gender||Smoking Habits|
Driver mutations were detected in about 50% of EGFR-wt lung ADC patients. Such alterations could represent potential targets for therapy and could be evaluated in routine multiplexed testing to obtain a wider tumor molecular characterization.
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Legal entity responsible for the study
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS
All authors have declared no conflicts of interest.