1279P - Targeting c-Met overexpression for acquired resistance to EGFR TKIs

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Lanying Gou
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors L. Gou1, J. Yang2, Y. Wu3, X. Zhang4
  • 1Division Of Pulmonary Oncology, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN
  • 2Cancer Center, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy Of Medical Sciences, Division of Pulmonary Oncology, 510080 - Guangzhou/CN
  • 3Division Of Pulmonary Oncology, Cancer Center,, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, 510080 - Guangzhou/CN
  • 4Medical Research Center, Cancer Center, Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou/CN

Abstract

Aim

c-Met amplification and T790M are both recognized as the common molecular mechanisms of acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in advanced non-small-cell lung cancer (NSCLC). It is not clear that c-Met overexpression could be as the biomarker for AR.

Methods

Advanced NSCLC patients with AR to EGFR TKIs were detected for c-Met overexpression by immunohistochemistry ≥50% tumor cells with moderate to high intensity staining were defined as c-Met positive. The statuses of EGFR, ALK, KRAS and ROS1 were also tested.

Results

From January 2013 to April 2014, 80 advanced NSCLC patients with AR to gefitinib or erlotinib were enrolled prospectively. The frequency of c-Met overexpression was 28.8% (23/80), c-Met overexpression + T790M 12.5% (10/80), T790M 25.0% (20/80), small-cell lung cancer or squamous cell transformation 2.5% (2/80), KRAS mutation 1.3% (1/80), ROS1 fusion 1.3% (1/80) and unknown mechanism 28.8% (23/80), respectively. Fourteen c-Met overexpressed patients received gefitinib plus c-Met inhibitors. Among them 4 patients with c-Met overexpression only shown good response to crizotinib (2/3 cases achieving partial response [PR] and 1 with stable disease), another case shown PR to single agent axitinib and all got prominently clinical benefit. Among 10 with c-Met overexpression + T790M, 6 received combination of EGFR TKI and c-Met inhibitor and best response was progressive disease, even though one was treated with afatinib plus crizotinib.

Conclusions

c-Met overexpression could be as a biomarker for AR. Combination of EGFR TKIs and c-Met inhibitor is a good strategy to overcome AR for c-Met overexpressed patients, but not effective in c-Met/T790M-coexisting cases, for whom further investigations are warranted.

Disclosure

All authors have declared no conflicts of interest.