Research Papers:

Low EGFR/MET ratio is associated with resistance to EGFR inhibitors in non-small cell lung cancer

Silvia Park, Emma Langley, Jong-Mu Sun, Steve Lockton, Jin Seok Ahn, Anjali Jain, Keunchil Park, Sharat Singh, Phillip Kim and Myung-Ju Ahn _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:30929-30938. https://doi.org/10.18632/oncotarget.5131

Metrics: PDF 988 views  |   HTML 1086 views  |   ?  


Silvia Park1,*, Emma Langley2,*, Jong-Mu Sun1, Steve Lockton2, Jin Seok Ahn1, Anjali Jain2, Keunchil Park1, Sharat Singh2, Phillip Kim2, Myung-Ju Ahn1

1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Prometheus Laboratories Inc, A Nestlé Health Science Company, Department of Research and Development, San Diego, CA, USA

*These authors have contributed equally to this work

Correspondence to:

Myung-Ju Ahn, e-mail: silkahn@skku.edu

Phillip Kim, e-mail: pkim@prometheuslabs.com

Keywords: NSCLC, EGFR TKI, PFS, EGFR/MET ratio, HER3

Received: April 07, 2015     Accepted: August 19, 2015     Published: September 03, 2015


Purpose: Although activating mutations in the epidermal growth factor receptor (EGFR) gene are predictive markers for response to EGFR inhibitors, 30–40% of EGFR-mutant non-small cell lung cancer (NSCLC) patients are de novo non-responders. Hence, we sought to explore additional biomarkers of response.

Methods: We conducted a prospective pilot study to characterize the expression and/or activation of key receptor tyrosine kinases (RTKs) in stage IIIB-IV NSCLC tumors. A total of 37 patients were enrolled and 34 underwent EGFR inhibitor treatment.

Results: As expected, patients bearing activating EGFR mutations showed increased progression free survival (PFS) compared to patients with wild-type EGFR status (9.3 vs 1.4 months, p = 0.0629). Analysis of baseline tumor RTK profiles revealed that, regardless of EGFR mutation status, higher levels of EGFR relative to MET correlated with longer PFS. At multiple EGFR/MET ratio cut-offs, including 1, 2 and 3, median PFS according to below vs. above cut-offs were 0.4 vs. 6.1 (p = 0.0001), 0.5 vs. 9.3 (p = 0.0006) and 1.0 vs. 11.2 months (p = 0.0008), respectively.

Conclusion: The EGFR/MET ratio measured in tumors at baseline may help identify NSCLC patients most likely to benefit from prolonged PFS when treated with EGFR inhibitors.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 5131