Frequency of driver mutations in EGFR wt NSCLC using mass spectrometry: Experience of Area Vasta Romagna

Background

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.

Methods

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.

Results

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.