1692P - Correlation of WTEGFR activation assessed by mab806 binding and EGFR kinase mutations in stage IIIA N2 NSCLC
|Date||30 September 2012|
|Event||ESMO Congress 2012|
|Session||Poster presentation II|
|Topics|| Lung and other Thoracic Tumours
|Presenter||Mun Sem Liew|
M.S. Liew1, C. Murone2, M. Walkiewicz2, P. Mitchell3, H.K. Gan3, S. Barnett4, P. Russell5, G. Wright6, A. Scott2, T. John3
The epidermal growth factor receptor (EGFR) pathway is a regulator of cellular proliferation and tumour progression. EGFR overexpression occurs with gene amplification and activating EGFR kinase mutations (EGFRmt). Monoclonal antibody 806 (mAb806) is an anti-EGFR antibody which targets tumours with EGFR mutation variant III and overexpression but not cells with low EGFR expression (wild type EGFR, wtEGFR) and normal tissues. To characterise mAb806 binding, we correlated mAb806 expression with EGFRmt, EGFR immunohistochemical (IHC) expression and overall survival (OS). Formalin fixed paraffin embedded tissues were stained using the mAb806 (Ludwig Institute for Cancer Research) and EGFR (Dako, PharmDx kit). A H-score was obtained based on staining intensity and percentage of cells stained. mAb806 H-scores 0-50 were classified as negative (mAb806-) and ≥50 as positive expression (mAb806+). EGFR H-scores were calculated to stratify patients into low (Dako score <200) and high (≥200, EGFR≥200) expressors. DNA was isolated and assayed using Sequenom's OncoCarta panel. Clinicopathological features were correlated with mAb806 status using Fisher's exact test and the log-rank test. Harzard ratios were calculated using the Mantel-Haenszel method. Of 107 patients with non-small cell lung carcinomas (NSCLC), 94 (88%) expressed EGFR (EGFR+), of which 24 (26%) patients were EGFR≥200 expressors. Forty of 107 (37%) were EGFR+ and mAb806 + , while 19 (18%) were EGFR≥200 and mAb806+. Squamous cell carcinomas (SqCC) were more likely to express mAb806+ than adenocarcinomas [16 of 29 (55%) vs 18 of 60 (30%); p = 0.0353]. Of the 15 patients with activating EGFRmt, 14 (93%) were mAb806 + , and 1 was mAb806- (p = 0.0001). Six of 15 (40%) EGFRmt and 15 of 81 (19%) wtEGFR tumours were EGFR≥200 expressors (p = 0.1895). Of 107 patients, OS was similar in both mAb806+ and mAb806- cases. In patients with SqCC, mAb806+ was associated with significantly poorer survival than mAb806- tumours (HR 2.82, 95%CI 1.13-7.04; p = 0.02). mAb806+ was associated with EGFRmt but was not prognostic in adenocarcinomas. mAb806+ in SqCC was associated with a poorer prognosis. Given its use as a therapeutic target and its potential role as a prognostic biomarker, further studies exploring the treatment efficacy of mAb806 in NSCLC are warranted.Disclosure
A. Scott: A.S is an inventor of a patent for mAb806, and a consultant to Life Science Pharmaceuticals which has the license for mAb806.
All other authors have declared no conflicts of interest.