446PD - Second-line afatinib vs erlotinib for patients with squamous cell carcinoma of the lung in LUX-Lung 8: analysis of tumor and serum biomarkers

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Thoracic cancers
Topics Cytotoxic agents
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Ki Hyeong Lee
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors K.H. Lee1, J. Soria2, E. Felip3, M. Cobo4, S. Lu5, K. Syrigos6, E. Goker7, V. Georgoulias8, W. Li9, S. Guclu10, D. Isla11, A. Ardizzoni12, S.M. Gadgeel13, N. Dupuis14, N.J. Gibson15, N. Krämer16, C. Bühnemann15, F. Solca17, E. Ehrnrooth18, G. Goss19
  • 1Medical Oncolgy, Chungbuk National University Hospital, 28644 - Cheong-ju/KR
  • 2Medical Oncology, Gustave Roussy Cancer Campus and University Paris-Sud, Paris/FR
  • 3Medical Oncology, Vall d’ Hebron University Hospital, Barcelona/ES
  • 4Medical Oncology, Hospital Carlos Haya, Malaga/ES
  • 5Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai/CN
  • 6Medical Oncology, Athens School of Medicine, Athens/GR
  • 7Medical Oncology, Ege University Faculty of Medicine, Izmir/TR
  • 8Medical Oncology, University Hospital of Heraklion, Heraklion/GR
  • 9Cancer Centre, First Hospital Affiliated to Jilin University, Changchun/CN
  • 10Chest Disease, Izmir Chest Diseases Research Hospital, Izmir/TR
  • 11Medical Oncology, Hospital Lozano Blesa, Zaragoza/ES
  • 12Medical Oncology, University Hospital, Bologna/IT
  • 13Medical Oncology, Karmanos Cancer Institute/Wayne State University, Detroit/US
  • 14Clinical Research, Biodesix Inc., Boulder/US
  • 15Translational Medicine And Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/DE
  • 16Biostatistics, Staburo GmbH, Munich, Germany on behalf of Boehringer Ingelheim Pharma GmBH & Co. KG, Biberach/DE
  • 17Pharmacology And Translational Research, Boehringer Ingelheim RCV GmbH & Co KG, Vienna/AT
  • 18Ta Oncology, Boehringer Ingelheim, Danmark A/S/DK
  • 19Medical Oncology, University of Ottawa, Ottawa/CA



In LUX-Lung 8 (LL8), second-line afatinib (A) significantly improved PFS and OS vs erlotinib (E) in patients (pts) with squamous cell carcinoma of the lung (N = 795). We report exploratory molecular analyses (n = 245) and immunohistochemistry (IHC; n = 288) of LL8 tumor samples to assess frequency of short variants (SVs) and copy number alterations (CNAs) in cancer-related genes, and clinical utility of genomic alterations or EGFR expression levels as predictive biomarkers. We also assessed the predictive utility of the prospectively validated VeriStrat® (VS) test, a serum protein test (n = 675).


Tumor samples were analyzed by FoundationOne™ next-generation sequencing. EGFR positivity (by IHC) was defined as staining in ≥ 10% of cells (Method 1) or H-score ≥200 (Method 2). Pretreatment serum samples were assigned as VS-Good (VS-G) or VS-Poor (VS-P) by mass spectrometry signature. Cox regression analysis was used to correlate PFS/OS with genomic alterations (individual or grouped, e.g. ErbB family), EGFR expression, and VS status.


The frequency of ErbB family alterations was low (SVs: EGFR 6.5%, HER2 4.9%, HER3 6.1%, HER4 5.7%; CNAs: EGFR 6.9%, HER2 3.7%). No individual genetic or ErbB family alterations were predictive of PFS/OS. Treatment (tx) benefit from A vs E was consistent in all molecular subgroups. EGFR expression was not predictive of PFS/OS benefit (Table). PFS and OS were improved (p 


No biomarkers were identified that predicted benefit with A over E in LL8 pts. A is a tx option in this setting irrespective of tumor characteristics. However, pt outcome strongly depends on VS status.rn

Table: 446PD

PFS and OS in patients assessed by IHC and VeriStrat
HR95% CIHR95% CI
IHC Method 1
EGFR + (A: 82%; E: 86%)0.760.57–1.020.840.63–1.12
EGFR– (A: 18%; E: 14%)0.870.45–1.680.770.40–1.51
IHC Method 2
EGFR + (A: 28%; E: 37%)0.780.47–1.300.690.42–1.13
EGFR– (A: 72%; E: 63%)0.760.55–1.050.690.42–1.13
VS-G vs VS-P0.650.54–0.770.410.35–0.49
A vs E (VS-G group)0.730.59–0.920.790.63–0.98
A vs E (VS-P group)0.970.73–1.270.900.70–1.16

Clinical trial indentification


Legal entity responsible for the study



Boehringer Ingelheim


J-C. Soria: Honoraria: BI, Roche. E. Felip: Honoraria: Boeheringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene Consultancy/Advisory board: Boeheringer Ingelheim, MSD, Eli Lilly, Roche, Pfizer, Novartis, BMS, Celgene Speakers bureau: BMS, Novartis, Roche. A. Ardizzoni: Advisory board: BI Honoraria: BMS, MSD. S.M. Gadgeel: Advisory board: Boehringer-Ingelheim, Genentech/Roche, Astra-Zeneca. N. Dupuis: Employment Biodesix, Inc. Stock ownership or options Biodesix, Inc. N.J. Gibson, N. Krämer: Employment: Boehringer Ingelheim Pharma GmbH & Co. KG. C. Bühnemann: Employment: BI. F. Solca: Employment: Boehringer Ingelheim RCV GmbH & Co KG. E. Ehrnrooth: Employment: Boehringer Ingelheim. G. Goss: Advisory board: AstraZeneca, Boehringer Ingelheim, BMS, Pfizer Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Pfizer. All other authors have declared no conflicts of interest.