Oncotarget

Research Papers:

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

Martin Faehling _, Birgit Schwenk, Sebastian Kramberg, Robert Eckert, Anna-Lena Volckmar, Albrecht Stenzinger and Jörn Sträter

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Oncotarget. 2017; 8:77897-77914. https://doi.org/10.18632/oncotarget.20857

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Abstract

Martin Faehling1, Birgit Schwenk1, Sebastian Kramberg1, Robert Eckert2, Anna-Lena Volckmar3, Albrecht Stenzinger3,* and Jörn Sträter4,*

1Department of Cardiology and Pneumology, Hospital Esslingen, Esslingen, Germany

2Outpatient Cancer Treatment Clinic Esslingen, Esslingen, Germany

3Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany

4Institute of Pathology Esslingen, Esslingen, Germany

*These authors have contributed equally to this work

Correspondence to:

Martin Faehling, email: [email protected]

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 1st and 2nd-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 3rd-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.


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