1222O - A randomized, open-label, phase III trial of afatinib (A) vs erlotinib (E) as second-line treatment of patients (pts) with advanced squamous cell c...

Date 27 September 2014
Event ESMO 2014
Session NSCLC, metastatic 1
Topics Anticancer Agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Glenwood Goss
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors G. Goss1, E. Felip2, M. Cobo3, S. Lu4, K.N. Syrigos5, K.H. Lee6, E. Göker7, V. Georgoulias8, W. Li9, D. Isla10, A. Morabito11, S.Z. Guclu12, Y.J. Min13, A. Ardizzoni14, S. Gadgeel15, J. Love16, V. Chand17, J. Soria18
  • 1Division Of Medical Oncology, University of Ottawa, K1H8L6 - Ottawa/CA
  • 2Oncology, Vall d'Hebron University Hospital, Barcelona/ES
  • 3Medical Oncology, Hospital Regional Universitario Carlos Haya, 29010 - Malaga/ES
  • 4Shanghai Lung Cancer Center, Shanghai Chest Hospital affiliated to Jiao Tong University School of Medicine, 20030 - Shanghai/CN
  • 5Oncology Unit, 3rd Department Of Medicine, Athens School of Medicine, GR-115 27 - Athens/GR
  • 6Oncology, Chungbuk National University Hospital, Chungcheongbuk-Cheongju/KR
  • 7Medical Oncology, Ege University Faculty of Medicine, TR-35100 - Izmir/TR
  • 8Medical Oncology, University General Hospital of Heraklion, GR-711 10 - Heraklion/GR
  • 9Oncology, First Hospital Affiliated to Jilin University, Changchun/CN
  • 10Servicio De Oncologia, Hospital Lozano Blesa, ES-50009 - Zaragoza/ES
  • 11Clinical Trials Unit, Istituto Nazionale Tumori Fondazione G Pascale - IRCCS, 80131 - Napoli/IT
  • 12Oncology, Seren Chest Diseases Surgery Hospital, Izmir/TR
  • 13Division Of Hematology/oncology, Ulsan University Hospital, Ulsan/KR
  • 14Medical Oncology, University Hospital, Parma/IT
  • 15Oncology, Wayne State University, Detroit/US
  • 16Biometrics And Data Management, Boehringer Ingelheim Corporation, Ridgefield/US
  • 17Clinical Development, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield/US
  • 18Dept. Of Medicine, Gustave Roussy Cancer Campus, 94805 - Paris/FR




A is an irreversible ErbB family blocker that has shown promising clinical activity in pts with SCC of the head/neck and lung. Here, we report results of LL8, a phase III trial that prospectively compared A and E in pts with SCC of the lung following failure of first-line chemotherapy.


Eligible pts with stage IIIB/IV SCC were randomized 1:1 to receive A (40 mg/day; 50 mg/day from Cycle 2 for pts meeting AE criteria) or E (150 mg/day) until disease progression. All pts had progressed after ≥4 cycles of platinum-based doublet chemotherapy and had not received prior EGFR TKIs. Pts were stratified based on race (eastern Asian vs other). The trial was powered for PFS and OS. The primary endpoint was PFS (RECIST 1.1) as assessed by independent radiological review (IRR). Secondary endpoints included overall survival (OS; planned at 632 events), objective response rate (ORR), disease control rate (DCR) and safety. Overall 795 pts were recruited between March 2012 and January 2014. Planned primary analysis was based on 414 PFS events by IRR in the first 669 patients randomized (A: 335, E: 334) while recruitment was ongoing.


Baseline characteristics were well balanced between arms: median age 65y; male 85%; eastern Asian 22%; never smoker 5%. Median PFS was significantly higher for A than E, both by IRR (2.4 vs 1.9 months; HR [95% CI]: 0.82 [0.68–1.00]; p = 0.043) and investigator review (2.7 vs 1.9 months; HR [95% CI]: 0.78 [0.65–0.93]; p = 0.005). Furthermore, ORR (4.8% vs 3.0%; p = 0.233) and DCR (45.7% vs 36.8%; p = 0.020) were higher with A vs E. Overall AE profile was comparable (pts with ≥G3 AEs: 50.2 and 49.1% for A and E) with higher incidence of drug-related ≥G3 diarrhoea (9.7 vs 2.4%) and G3 stomatitis (3.3 vs 0.0%) with A and higher incidence of G3 rash/acne with E (5.5 vs 9.0%).


LL8 is the largest prospective trial to compare EGFR TKIs in pts with relapsed/refractory SCC. PFS and DCR were significantly better for A than E. AEs were comparable and consistent with the mechanistic profile of EGFR inhibition.


G. Goss: Advisory board for Boehringer Ingelheim prior to initiation of study; E. Felip: Advisory Boards for: Boehringer Ingelheim, Novartis, Roche and Bristol Myers Squibb; S. Lu: Advisory Boards for: AstraZeneca and Boehringer Ingelheim; K.N. Syrigos: Advisory boards for Roche, Novartis and Leo; A. Morabito: Advisory Boards for: Lilly and Italfarmaco; A. Ardizzoni: Advisory Boards for: Boehringer Ingelheim, MSD, BMS, Lilly, GSK, Daiichi, Pierre Fabre, Pfizer; S. Gadgeel: Advisory Boards for: BI, Novartis and Genentech; J. Love: Employee of Boehringer Ingelheim; V. Chand: Employee of Boehringer Inhelheim J. Soria: Advisory Boards for: Boehringer Inhelheim. All other authors have declared no conflicts of interest.