1339 - Impact of EGFR mutation status on clinical benefit from BIBW 2992 in patients (pts) with advanced non-small cell lung cancer (NSCLC) progressing aft...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter Jens Köhler
Authors J. Köhler1, K. Worm2, T.C. Gauler3, M. Hoiczyk4, D. Theegarten2, W.E.E. Eberhardt5, J. Hense6, F. Breitenbuecher4, K.W. Schmid2, M. Schuler4
  • 1Internal Medicine (cancer Research), West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 2Department Of Pathology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 3Dept. Of Medicine (cancer Research), West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 4Department Of Medical Oncology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 5Dept. Medical Oncology, West German Cancer Center, University Hospital Essen, 45122 - Essen/DE
  • 6Dept. Int. Medicine (cancer Research), West German Cancer Center, University Hospital Essen, 45122 - Essen/DE

Abstract

Background

The reversible EGFR tyrosine kinase inhibitors E and G are effective treatments for advanced NSCLC, but most pts acquire resistance. Currently, the benefit from sustained EGFR blockade during subsequent salvage therapy is unclear. LUX-Lung 5 is an international, multicenter phase III trial studying the efficacy of BIBW2992 (Afatinib®, A), an irreversible erbB family blocker, in NSCLC pts progressing after treatment with ctx and E or G irrespective of their EGFR mutation status. Here we report the outcome of NSCLC pts treated within LUX-Lung 5 at a single center in relation to EGFR and KRAS mutation status.

Methods

Pts with stage IV (UICC 7) NSCLC progressing after ctx and E or G were enrolled into LUX-Lung 5. In part A of the study pts received A (starting dose 50 mg/d) until progression. In part B pts with clinical benefit ≥12 wks were randomized between A plus weekly paclitaxel vs investigator's choice mono ctx. Following microdissection, tumor DNA was extracted and analyzed by PCR and Sanger sequencing.

Results

Between May 2010 and February 2011 39 pts (20 f, 19 m; median age 61 y, 38-83 y) were enrolled at the West German Cancer Center. Median number of pretreatments was 3 (1-8) including E or G. So far, tumor biopsies were retrieved from 25 pts (64%). Somatic EGFR mutations were detected in 11 pts (44% of analyzed tumors, 28% of entire cohort), whereas 14 pts (56%/36%) exhibited EGFR wild type (wt) sequences. EGFR mutation status remains unknown in 14 pts (36%). KRAS mutation analysis was performed in 20 pts (51% of entire cohort) and 4 mutations were observed (20%/10%), 3 in EGFR wt and one in an EGFR mutant tumor. Median survival time from initiation of A was 432 d in EGFR mutant pts, 189 d in EGFR wt pts, and 255 d in KRAS mutant pts. Median survival time of pts with unknown EGFR mutation status was 191 d. Safety of A was manageable.

Conclusions

A can achieve disease control in heavily pretreated NSCLC pts. Pts with EGFR mutant tumors experience prolonged survival as compared to EGFR wt tumors (HR 0.29; 95% CI 0.07–0.64; p = 0.0058). This argues for sustained tumor dependency on EGFR signaling despite progression after E or G.

Disclosure

J. Köhler: J. Köhler received financial support from Boehringer Ingelheim for writing a review article.

T.C. Gauler: T.C. Gauler is principle investigator of the BI1200.43 trial testing Afatinib in HNSCC.

D. Theegarten: D. Theegarten is member of the Lilly Advisory Board.

W. Eberhardt: W. Eberhardt received honoraries for advisory board functions from Boehringer Ingelheim, Astra Zeneca, Roche, OSi Pharmaceuticals, Pfizer and honoraries for lectures from Boehringer Ingelheim, Astra Zeneca, Roche and Pfizer.

M. Schuler: M. Schuler received research funding from Boehringer Ingelheim and travel support from Lilly.

All other authors have declared no conflicts of interest.