86O - Afatinib (A) plus cetuximab (C) in the treatment of patients (pts) with NSCLC: The story so far

Date 06 May 2017
Event ELCC 2017
Session Targeted therapies and management of brain metastasis
Topics Immunotherapy
Thoracic malignancies
Non-small-cell lung cancer
Presenter Leora Horn
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors E. Smit1, J. Soria2, Y.Y. Janjigian3, H.J.M. Groen4, W. Pao5, E. Calvo6, A. Gazzah2, J. Fan7, M. Ould-Kaci7, L. Horn8
  • 1Department Of Pulmonary Diseases, VU University Medical Center, 1007 MB - Amsterdam/NL
  • 2Drug Development Department, Gustave Roussy Cancer Campus and University Paris-Sud, Villejuif/FR
  • 3Department Of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York/US
  • 4Department Of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen/NL
  • 5Department Of Medicine, Vanderbilt-Ingram Cancer Center, Nashville/US
  • 6Medical Oncology Division, START Madrid, Centro Integral Oncológico Clara Campal, Madrid/ES
  • 7Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield/US
  • 8Department Of Medicine, Vanderbilt Ingram Cancer Center, Nashville/US



Constitutive EGFR signalling due to activating mutations (e.g. EGFRm+ NSCLC) or overexpression (e.g. squamous (sq) NSCLC) is a common mechanism of tumourigenesis. There is biological rationale for combining A + C in tumours with unmet medical need, e.g. EGFRm+ NSCLC with resistance to EGFR-TKIs, and in advanced sqNSCLC. Preclinically, A + C improved anti-tumour activity in EGFRm+ NSCLC vs A or C alone. Here we report outcomes from two Phase Ib studies of A + C: NCT01090011 (study 1) in pts with EGFRm+ NSCLC resistant to gefitinib/erlotinib (G/E); and NCT02020577 (study 2) in unselected pts with heavily pretreated advanced solid tumours, including sqNSCLC.


Study 1 comprised a dose-finding phase to identify the maximum tolerated dose (MTD) of A + C, and an expansion phase (EP) in which 126 pts received the MTD of A 40 mg/day + C 500 mg/m2 Q2W. In study 2, 9 pts received A + C in a dose-escalation phase, and a further 49 pts received the MTD of A 40 mg/day + C 250 mg/m2/week in an EP, including 12 pts with sqNSCLC.


Drug-related adverse events (DR-AEs; all grades) were reported in 99% of pts in the EP of study 1 (n = 126), and 98% of pts in study 2 (n = 58). Grade 3/4/5 DR-AEs were experienced by 44%/2%/2% of pts in study 1 and 31%/3%/0% in study 2. DR-AEs led to discontinuation of treatment in 14% of pts in study 1 and 12% in study 2. Efficacy in pts with NSCLC is shown in the table. In the study 1 EP, ORR was 29% and median PFS was 4.7 months; there were no significant differences in ORR or median PFS in pts with T790M+ vs T790M- tumours (32 vs 25% [p = 0.341] and 4.6 vs 4.8 months [p = 0.643], respectively). Median duration of OR was 5.7 months. In the study 2 EP, 75% of pts with sqNSCLC had SD, and median PFS was 11.9 weeks.


Based on the demonstrated antitumour activity and a predictable/manageable safety profile, A + C may be a treatment option in pts with EGFRm+ NSCLC and acquired resistance to G/E (irrespective of T790M status) or with pre-treated advanced sqNSCLC. rnTable: 86O

Efficacy outcomes

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
Study 1 expansion phase1 (n = 126)Study 2 expansion cohort2 (n = 12)
Disease control (CR/PR/SD), n (%)89 (71)9 (75)
OR (CR/PR), n (%)37 (29)0
SD52 (41)9 (75)
Unconfirmed OR5 (4)
PD, n (%)27 (21)3 (25)
Median duration of OR, months (range)5.7 (1.8–24.4)
Median duration of disease control, weeks (standard deviation)17.9 (9.9)
Median PFS (95% CI)4.7 months (4.3–6.4)11.9 weeks (5.1–19.4)

CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease;


OR, objective response; PFS, progression-free survival 1. Janjigian YY, et al. Cancer Discov 2014;4:1036-45 2. Gazzah A, et al. Eur J Cancer 2016;68(Suppl. 1);S139:abstract 426


Clinical trial identification

NIH study numbers: 1200.71: NCT01090011 1200.122: NCT02020577

Legal entity responsible for the study

Boehringer Ingelheim


Boehringer Ingelheim


J-C. Soria: Astrazeneca, Astex, GSK, Gammamabs, Eli Lilly, MSD, Merus, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Symphogen, Takeda. Y.Y. Janjigian: Employee of Memorial Sloan Kettering Cancer Center Advisory boards: ASCO GI Corporate-sponsored research: Merck, BMS Consultant: Pfizer Grant/research: BI, Bayer, Amgen, Genentech, Roche. H.J.M. Groen: Participated on advisory boards for Boehringer Ingelheim. W. Pao: Reports that patent rights on EGFR T790M were licensed by MSKCC to Molecular MD. J. Fan: Boehringer Ingelheim employee. M. Ould-Kaci: Employee of Boehringer Ingelheim. L. Horn: Consulting for AbbVie, BMS, Merck, Eli Lilly, Xcovery, Bayer. All other authors have declared no conflicts of interest.