1199PD - Prevalence and clinical outcomes for patients with MET protein expression in patients with non-small cell lung cancer in Europe: Results from the E...

Date 29 September 2014
Event ESMO 2014
Session NSCLC, metastatic
Topics Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Lukas Bubendorf
Citation Annals of Oncology (2014) 25 (suppl_4): iv417-iv425. 10.1093/annonc/mdu348
Authors L. Bubendorf1, O. Dafni2, V. Tischler3, S. Finn4, W. Biernat5, E. Verbeken6, H. Hager7, N. Murtra8, E. Thunnissen9, D. Nonaka10, A. Warth11, E.J. Speel12, S. Savic1, M. Martorell13, Z. Tsourti2, K. Schulze14, A. Das-Gupta15, K. Kerr16, S. Peters17, R.A. Stahel18
  • 1Institute For Pathology, University Hospital Basel, 4031 - Basel/CH
  • 2Etop Statistical Center, Frontier Science Foundation-Hellas, Athens/GR
  • 3Departments Of Pathology, University Hospital Zürich, Zürich/CH
  • 4Trinity College And St. James’s Hospital, University of Dublin, Dublin/IE
  • 5Department Of Pathology, Medical University of Gdansk, 80-214 - Gdansk/PL
  • 6Department Of Pathology, University Hospital Leuven, 3000 - Leuven/BE
  • 7Department Of Pathology, Aarhus University Hospital, 8000 - Aarhus/DK
  • 8Department Pathology, Vall d'Hebron University Hospital, Barcelona/ES
  • 9Department Of Pathology, Free University Medical Center, Amsterdam/NL
  • 10Departments Of Pathology, The Christie Hospital, and Institute of Cancer Sciences, The University of Manchester, M20 4BX - Manchester/GB
  • 11Department Of Pathology, Universitätsklinikum Heidelberg, Heidelberg/DE
  • 12Department Of Pathology, Maastricht University Medical Centre, 6229 HX - Maastricht/NL
  • 13Department Pathology, Hospital General Universitario de Valencia, 46014 - Valencia/ES
  • 14Oncology Biomarker Development, F. Hoffmann-LaRoche Ltd, Basel/CH
  • 15Oncology, F. Hoffmann-La Roche Ltd, CH-4070 - Basel/CH
  • 16Department Of Pathology, Aberdeen Royal Infirmary, Aberdeen/GB
  • 17Etop, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne/CH
  • 18Etop And Clinic Of Oncology, University Hospital Zürich, 8091 - Zürich/CH

Abstract

Aim

The reported prevalence of MET overexpression varies from 25-55% in non-small cell lung cancer (NSCLC) and clinical correlations are emerging slowly. In a well-defined NSCLC cohort of the Lungscape program, we explore the epidemiology, the natural history of IHC MET positivity and its association to OS, RFS and TTR.

Methods

Resected stage I-III NSCLC identified based on the quality of clinical data and FFPE tissue availability were assessed for MET expression using immunohistochemistry (IHC) on TMAs (CONFIRM anti total c-MET assay, clone SP44, Ventana BenchMark platform). All cases were analysed at participating pathology laboratories using the same protocol, after passing an external quality assurance program. MET positive status is defined as ≥ 50% of tumor cells staining with 2+ or 3+ intensity.

Results

A total of 2709 cases are included in the iBiobank and will be analysed. IHC MET expression is currently available for 1552 patients, with positive MET IHC staining in 380 cases [24.5%; IHC 3+ in 157 cases (41.3%) and 2+ in 223 cases (58.7%)]. The cohort of 1552 patients includes 48.2%, 44.7% and 4.4% cases of adenocarcinoma, squamous and large cell histologies, respectively. IHC MET status was independent of stage, age and smoking history. Significant differences in MET positivity were associated with gender (32% vs. 21% for female vs. male, p < 0.001), with performance status (25% vs. 18% for 0 vs. 1-3, p = 0.006), and histology (34%, 14% and 24% for adenocarcinoma, squamous and large cell carcinoma, p < 0.001). IHC MET positivity was independent of the IHC ALK status (p = 0.08). At last FU, 52% of patients were still alive, with a median FU of 4.8 yrs. No association of IHC MET was found with OS, RFS or TTR.

Conclusions

The preliminary results for this large multicentre European cohort describe a prevalence of MET overexpression that seems lower than previous observations in NSCLC, such as reported for the OAM4971g trial, suggesting potential biological differences between surgically resected and metastatic disease. Analysis for the full cohort is ongoing and results will be presented.

Disclosure

L. Bubendorf: Disclosures: Stock ownership: Roche Advisory boards: Roche, Pfizer Research support: Roche; K. Schulze: Full time employee of Roche; A. Das-Gupta: I am a full time employee of Roche. All other authors have declared no conflicts of interest.