1227O - Activity of afatinib/cetuximab in patients (pts) with EGFR mutant non-small cell lung cancer (NSCLC) and acquired resistance (AR) to EGFR inhibitors

Date 30 September 2012
Event ESMO Congress 2012
Session NSCLC, metastatic I
Topics Cytotoxic agents
Non-small-cell lung cancer
Biological therapy
Presenter Yelena Janjigian
Authors Y.Y. Janjigian1, E.F. Smit2, L. Horn3, H.J.M. Groen4, R. Camidge5, S. Gettinger6, Y. Fu7, L.J. Denis8, V. Miller9, W. Pao10
  • 1Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Dept. Of Pulmonary Diseases, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL
  • 3Medicine, Vanderbilt University, Nashville/US
  • 4Pulmonary Diseases, University Hospital Groningen (UMCG), NL-9700 RB - Groningen/NL
  • 5University of Colorado Cancer Centre, Aurora/US
  • 6Thoracic Oncology Program, Yale University School of Medicine, New Haven/US
  • 7Clinical Trial Management, Boehringer Ingelheim, Ridgefield/US
  • 8Clinical Development And Medical Affairs, Boehringer Ingelheim, Ingelheim/DE
  • 9Clinical Development, Foundation Medicine, Cambridge/US
  • 10Hematology/oncology, Vanderbilt University, Nashville/US



AR to reversible epidermal growth factor receptor (EGFR)-specific tyrosine kinase inhibitors (TKIs) in EGFR mutant (mt) NSCLC is associated with an exon 20 EGFR T790M mutation in ∼50% of cases. The targeted combination of afatinib (A), a potent ErbB Family Blocker, and cetuximab (C), induced nearly complete regression in T790M transgenic murine models. Following determination of the maximum tolerated dose, early clinical data suggest that the recommended dose combination of A/C is tolerable, with encouraging activity in AR cases (Janjigian Y. J Clin Oncol 2011; 29 (suppl); abstr 7525). Here, we report safety and efficacy data from an expanded cohort in AR NSCLC.


Pts with EGFR mt advanced NSCLC – progressive on erlotinib or gefitinib – transitioned directly (interval minimum 3 days) to oral, daily A 40 mg and intravenous, bi-weekly C 500 mg/m2. Tumour biopsy after AR, prior to study therapy, was mandated by protocol. Efficacy endpoints included objective response (OR) and progression-free survival (PFS) with imaging at week 4, 8, 12 and every 8 weeks thereafter.


To date, 100 eligible pts have been treated (median duration 4.1 months, range 1–14+ months). EGFR del 19 and L858R mt were present in 63% and 31% of pts, and EGFR T790M mt in 53% of pts. Adverse events included rash (Grade 1/2: 65%; Grade 3: 12%) and diarrhoea (Grade 1/2: 63%; Grade 3: 6%). Ninety pts were evaluable for efficacy; rate of disease control was 94% and probability of PFS at 3, 6 and 9 months was 70, 42 and 18%, respectively. In the first 60 evaluable pts enrolled at least 6 months before data cut-off, the confirmed OR rate was 40% (95% CI: 27.6–53.5), similar in both T790M+ (38%) and T790M- (47%) tumours; the median PFS was 4.7 months and the median duration of response was 7.7 months.


Afatinib/cetuximab shows encouraging clinical efficacy in pts with AR to erlotinib or gefitinib, demonstrating that many EGFR mt NSCLCs continue to depend on ErbB signalling for survival. Efforts to elucidate the underlying mechanisms are ongoing, and updated clinical data will be presented. Further studies are planned to establish the potential role of this targeted combination in the treatment of EGFR mt NSCLC.


Y.Y. Janjigian: Research funding from Boehringer Ingelheim, INC.

L. Horn: Unpaid advisory board for OSI/Astellas/Genentech.

H.J.M. Groen: Research funding from Roche and Eli Lilly to the University Medical Centre.

D.R. Camidge: Consultancy and honoraria from BI; Research funding from Lilly.

Y. Fu: Employee of Boehringer Ingelheim.

L.J. Denis: Employee of Boehringer Ingelheim.

V. Miller: Foundation Medicine-employment, stockholder.

W. Pao: Consulting: MolecularMD, AstraZeneca, BMS, Symphony Evolution, Clovis Oncology; Research funding: Enzon, Xcovery, AstraZeneca, Symphogen, Clovis Oncology; Other: Rights to EGFR T790M testing licensed on behalf of self and others by MSKCC to MolecularMD.

All other authors have declared no conflicts of interest.