198P - Targeting de novo c-Met overexpression in advanced non-small-cell lung cancer

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter An-Na Li
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors A. Li1, J. Yang2, X. Zhang2, Q. Zhou3, Y. Wu4
  • 1Division Of Pulmonary Oncology, Cancer Center, Guangdong Lung Cancer Institute, 510080 - Guangzhou/CN
  • 2Division Of Pulmonary Oncology, Guangdong Lung Cancer Institute, 510080 - Guangzhou/CN
  • 3Guangdong General Hospital, Guangdong Academy Of Medical Sciences, Guangdong Lung Cancer Institute,, Guangdong/CN
  • 4Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, 510080 - Guangzhou/CN

Abstract

Aim

c-Met gene amplification has been identified as one of the acquired resistances to epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC). However, it is not clear that de novo c-Met overexpression could used be as a biomarker for resistance.

Methods

Advanced NSCLC patients with de novo c-Met expression were detected by immunohistochemistry (IHC). ≥50% tumor cells with moderate to high intensity staining were defined as c-Met positive.Gene copy numbers have been detected by fluorescence in situ hybridization (FISH). ≥5 copies were positive.The statuses of EGFR, ALK, KRAS and ROS1 were also tested.

Results

From January 2013 to April 2014, 101 advanced NSCLC patients with de novo c-Met overexpression were enrolled. The frequency of c-Met overexpression was 26.7% (27/101). For c-Met overexpressed patients, adenocarcinoma is 92.59% (25/27), squamous and adeno-squamous cancer was 3.7%. (1/27,1/27). Nine of the de novo c-Met positive patients received crizotinib treatment. Five of them achieved partial response (PR), 2 of them were stable disease (SD) and 2 were waiting for assessment of response, Table1. Adverse events of grade 3 QT prolongation have been found in 1 patient.

Objective response to crizotinib treatment for advanced NSCLC patients with de novo c-Met overexpression.

patient No. 1 2 3 4 5 6 7
sex Male Male Female Male Male Male Male
ECOG PS 2 3 2 1 3 1 3
IHC of c-Met 55% × 2 100% × 3 60% × 2 70% × 2 100% × 3 50% × 3 + 30% × 2 100% × 3
FISH of c-Met N/A + - - + - -
Line of crizotinib 4th 1st 3rd 1st 1st 2nd 2rd
Response PR PR PR SD PR SD PR

Conclusions

De novo c-Met overexpression could be as a biomarker. c-Met inhibitor against de novo c-Met overexpressed patients is a good strategy. IHC seems better than FISH in predicting efficacy for c-MET inhibitor.

Disclosure

All authors have declared no conflicts of interest.