Low EGFR/MET ratio is associated with resistance to EGFR inhibitors in non-small cell lung cancer
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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
Myung-Ju Ahn, e-mail: firstname.lastname@example.org
Phillip Kim, e-mail: email@example.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.
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