1272P - Relationship between EGFR expression level, EGFR mutation status and the efficacy of chemotherapy plus cetuximab in flex study patients with advance...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Translational Research
Non-small-cell lung cancer
Basic Principles in the Management and Treatment (of cancer)
Presenter Jean-Yves Douillard
Authors J. Douillard1, R. Pirker2, K.J. O'Byrne3, K. Kerr4, S. Störkel5, I. Celik6, A. von Heydebreck7, F.A. Shepherd8
  • 1Centre René Gauducheau, Institut de Cancerologie de l'Ouest, 44805 - St Herblain/FR
  • 2Medical University of Vienna, AT-1090 - Vienna/AT
  • 3Oncology, St James's Hospital, Dublin/IE
  • 4Department Of Pathology, Aberdeen Royal Infirmary, Aberdeen/UK
  • 5Institute Of Pathology, University of Witten/Herdecke and HELIOS Hospital Wuppertal, Wuppertal/DE
  • 6Global Research & Early Development, Merck KGaA, Darmstadt/DE
  • 7Global Biostatistics/biostatistics Oncology I, Merck KGaA, Darmstadt/DE
  • 8Department Of Medicine, Princess Margaret Hospital, Toronto/CA



Analysis of prospectively collected immunohistochemistry (IHC) data from the phase III FLEX study in advanced NSCLC showed that high EGFR expression (IHC score ≥200 [scale of 0–300]) is a tumor biomarker that can predict survival benefit from the addition of cetuximab to first-line vinorelbine/cisplatin chemotherapy (CT). Treatment outcome was analyzed further in FLEX study EGFR expression groups according to EGFR mutation status.


Tumors from patients (pts) in the FLEX intention to treat (ITT) population were screened for the presence of EGFR exon 18–21 mutations (excluding T790M) using the therascreen EGFR PCR Kit (Qiagen). Outcome according to treatment was assessed across key efficacy endpoints in high and low EGFR expression groups (IHC score ≥200 vs <200) in the context of EGFR mutation status (wild-type [WT] or mutant [Mut]).


Tumors from 970/1125 pts (86%) were evaluable for both EGFR expression and EGFR mutation status. Mutations were detected in 133/970 (14%) tumors (124/133 [93%] exon 19 deletions or L858R); 50/288 (17%) in the high EGFR expression group and 83/682 (12%) in the low EGFR expression group. In the high EGFR group a survival benefit for the addition of cetuximab to CT was demonstrated in pts with EGFR WT tumors (hazard ratio [HR] 0.76, 95% CI 0.57–1.00) with the magnitude of benefit similar to that of the high EGFR group of the ITT population (HR 0.73, 95% CI 0.58–0.93). Response was also higher in the CT + cetuximab arm for pts in this group with EGFR WT tumors (odds ratio 1.73, 95% CI 1.00–3.00). Pts in the high EGFR group with EGFR Mut tumors also seemed to benefit from CT + cetuximab in relation to survival (HR 0.86, 95% CI 0.40–1.84) and response (odds ratio 3.27, 95% CI 1.01–10.6) although numbers in this group were low. Outcome for the EGFR Mut subgroup with exon 19 deletion or L858R mutations will be presented.


In the high EGFR expression group pts with EGFR WT advanced NSCLC had a higher response rate and greater survival benefit from CT + cetuximab compared with CT alone. Benefit was also seen in pts with EGFR Mut tumors (exon 18–21) but firm conclusions cannot be drawn due to low pt numbers.


J. Douillard: AGENNIX: Advisor ASTRAZENECA: Advisor, speaker in symposia BOERHINGER-INGELHEIM: Advisor GSK: Advisor, speaker in symposia MERCK SERONO: Advisor, speaker in symposia, research grant PFIZER: Advisor ROCHE/GENENTECH: Advisor, speaker in symposia.

R. Pirker: The author declares the following: Honoraria for Advisory Board and speaker's fee from AstraZeneca, Boehringer Ingelheim, Merck Serono and Roche.

K.J. O'Byrne: The author declares: Payment from Merck Serono in relation to a protocol writing committee and advisory boards and travel costs in related to attendance. Honoraria from Merck Serono associated with presentation of data at satellite/company symposia.

K.M. Kerr: Keith Kerr has acted on Advisory Boards and has received speaker's fees from Merck Serono. He has had similar roles with Astra Zeneca, Roche, Eli Lilly, Daichi Sankyo, Pfizer, Boeringher Ingelheim and Glaxo Smith Klein.

S. Störkel: The author has been involved in sponsored research by Merck KGaA.

I. Celik: The author is an employee of Merck KGaA.

A. von Heydebreck: Teh author is an employee of Merck KGaA and declares stock ownership in this company.

F.A. Shepherd: Honorarium from Merck KGaA for presentation at Scientific, Industry-sponsored Satellite Symposium. Provided compensated consultation services to Merck KGaA.