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A. Dubini
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-005 - Frequency of Actionable Alterations in EGFR wt NSCLC: Experience of the Wide Catchment Area of Romagna (AVR) (ID 3934)
14:30 - 14:30 | Author(s): A. Dubini
- Abstract
Background:
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have improved the outcome of patients with EGFR-mutated lung adenocarcinoma (ADC). However, EGFR mutation occurred in about only 10-15% of ADC, but other alterations are emerging as potential target of drugs. We analyzed the frequency of potentially targetable driver alterations in a series of advanced EGFR-wild type (wt) NSCLC patients.
Methods:
724 advanced EGFR-wt NSCLC patients enrolled from the Wide Catchment Area of Romagna (AVR) 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 MassARRAY[®] (SEQUENOM[®] Inc, California). ERBB4 was evaluated by direct sequencing and EML4-ALK and ROS1 rearrangements were assessed by immunohistochemistry or fluorescence in situ hybridization.
Results:
331 (45.7%) patients showed at least one alteration. Of these, 72.2%, 6.3%, 3.6%, 1.8%, 2.1% and 1.2% patients had mutations in KRAS, BRAF, PIK3CA, NRAS, ERBB2 and MAP2K1 genes, respectively. Only one patient showed a mutation in ERBB4 gene. EML4-ALK and ROS1 rearrangements were observed in 4.3% and 1.4% of all patients, respectively. The distribution of mutations in relation to gender and smoking habits is reported in the Table. Overlapping mutations were observed in 7 KRAS-mutated patients: 2 (28.6%) patients were also mutated in PIK3CA, 4 (57.1%) showed also an EML4- ALK translocation and one (14.3%) had a ROS1 rearrangement. One (0.3%) patient showed both BRAF and PIK3CA alterations. Correlation analyses between the different mutations and patient outcome are ongoing.
*: some data are missingGENE Mutated Patients N (%) Gender Smoking Habits* Female (%) Male (%) Smoker (%) Never Smoker (%) KRAS 239 (33) 93 (39) 146 (61) 115 (48.1) 9 (3.8) BRAF 21 (3) 11 (52.4) 10 (47.6) 11 (52.4) 1 (4.8) NRAS 6 (0.8) 4 (66.7) 2 (33.3) 4 (66.7) - PIK3CA 12 (1.6) 4 (33.3) 8 (66.7) 5 (41.7) - MAP2K1 4 (0.5) - 4 (100) 1 (25) - ERBB2 7 (0.9) 5 (71.4) 2 (28.6) - 1 (14.3) EML4-ALK 31 (4.3) 20 (64.5) 11 (35.5) 12 (38.7) 8 (25.8) ROS1 10 (1.4) 7 (70) 3 (30) 3 (30) 5 (50)
Conclusion:
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.
