Oncogenic driver mutations, treatment, and EGFR-TKI resistance in a Caucasian population with non-small cell lung cancer: survival in clinical practice

// Martin Faehling 1 , Birgit Schwenk 1 , Sebastian Kramberg 1 , Robert Eckert 2 , Anna-Lena Volckmar 3 , Albrecht Stenzinger 3, * and Jorn Strater 4, * 1 Department of Cardiology and Pneumology, Hospital Esslingen, Esslingen, Germany 2 Outpatient Cancer Treatment Clinic Esslingen, Esslingen, Germany 3 Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany 4 Institute of Pathology Esslingen, Esslingen, Germany * These authors have contributed equally to this work Correspondence to: Martin Faehling, email: m.faehling@klinikum-esslingen.de Keywords: NSCLC, EGFR, ALK, BRAF, overall survival Received: April 18, 2017     Accepted: July 06, 2017     Published: September 13, 2017 ABSTRACT Introduction : Oncogenic driver mutations activating EGFR , ALK , or BRAF in NSCLC predict sensitivity to specific tyrosine-kinase inhibitors (TKIs). We provide data on prevalence, treatment and survival of driver-mutation positive NSCLC in a predominantly Caucasian population in routine clinical practice. Patients and Methods : NSCLC patients diagnosed from 2006-2015 with an EGFR-test result were included (n=265). Testing for EGFR , ALK , or BRAF was performed if specific TKI therapy was considered. Case-control analyses of overall survival (OS) comparing driver-mutation positive and negative patients were performed. Results : 44 sensitizing EGFR mutations (17%), 8 ALK translocations (7%, n=111) and 3 BRAF mutations (8%, n=39) were detected in adenocarcinoma or adenosquamous carcinoma. We did not find mutations in tumors without an adenocarcinoma-component. More than 90% of inoperable driver-mutation positive patients received TKI-therapy. Case-control analysis revealed improved OS of driver-mutation positive patients (39.6 vs. 19.4 months, HR 0.51). OS was improved in stage IV patients but not in stage I-III patients. OS of EGFR-TKI treated patients was similar for 1 st and 2 nd -line EGFR-TKI treatment. Patients not treated with EGFR-TKI had no benefit in OS. Re-biopsies obtained at progression revealed an EGFR -T790M mutation in 73% (n=11). These patients responded to the 3 rd -generation EGFR-TKI osimertinib. Discussion : Testing guided by predictive clinical parameters resulted in twice as high rates of mutation-positive patients than expected, and TKI treatment resulted in a strong long-term OS advantage. Conclusion: Testing for driver mutations is feasible in routine clinical practice, and identifies patients who benefit from TKI-therapy. OS compares favorably with OS in clinical studies.