Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status

Kalikaki, Aristea; Koutsopoulos, Anastasios; Hatzidaki, Dora; Trypaki, Maria; Kontopodis, Emmanouel; Stathopoulos, Efstathios; Mavroudis, Dimitris; Georgoulias, Vassilis; Voutsina, Alexandra

doi:10.1016/j.lungcan.2009.09.010

« Previous Next »Lung Cancer
Volume 69, Issue 1 , Pages 110-115, July 2010

Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status

Aristea Kalikaki
- Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece
Anastasios Koutsopoulos
- Department of Pathology, University General Hospital of Heraklion, Crete, Greece
Dora Hatzidaki
- Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece
Maria Trypaki
- Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece
Emmanouel Kontopodis
- Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece
Efstathios Stathopoulos
- Department of Pathology, University General Hospital of Heraklion, Crete, Greece
Dimitris Mavroudis
- Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece
- Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece
Vassilis Georgoulias
- Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece
- Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece
Alexandra Voutsina
- Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece
- Corresponding author at: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, PO Box 1352, 711 10 Heraklion, Crete, Greece. Tel.: +30 2810 3945 78; fax: +30 2810 3945 82.

Received 4 May 2009; received in revised form 29 July 2009; accepted 28 September 2009. published online 26 October 2009.

Abstract

Background

Somatic mutations in EGFR and K-RAS may predict for sensitivity and resistance to EGFR tyrosine kinase inhibitors (TKIs). Whether EGFR and K-RAS mutations could also predict clinical outcome of non-small cell lung cancer (NSCLC) patients following front-line chemotherapy has not yet been established.

Patients and methods

One hundred and sixty-two chemotherapy-naïve patients with locally advanced/metastatic NSCLC who received front-line chemotherapy were included in this retrospective study and their clinical outcome data was analyzed according to EGFR and K-RAS mutation status of their tumors.

Results

Classical activating EGFR and K-RAS mutations were found in 8.2 and 22.6% of patients respectively and were not associated with patients’ clinicopathological characteristics. Patients with classical EGFR mutations had a higher probability of response to front-line chemotherapy as compared to those with wild type EGFR (p=0.023). Multivariate analysis showed that the presence of activating EGFR mutations was an independent factor associated with response to front-line chemotherapy (HR=4.85; 95% CI: 1.13–20.83, p=0.034). K-RAS mutation status was not associated with response to front-line chemotherapy. The presence of activating EGFR but not of K-RAS mutations was associated with a significantly higher overall survival compared to patients without mutations treated with platinum-based front-line chemotherapy (p=0.043).

Conclusions

The data indicate that EGFR mutation status could be predictive for response to cytotoxic front-line chemotherapy in patients with NSCLC. Additional prospective studies are needed in order to validate this observation and to define whether these patients should be preferentially treated with front-line TKIs or chemotherapy.

Keywords: NSCLC, K-RAS mutations, Front-line chemotherapy, EGFR mutations, TKIs