108PD - Afatinib (A) vs erlotinib (E) as second-line treatment of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following first-lin...

Date 16 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Glenwood Goss
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors G.D. Goss1, E. Felip2, M. Cobo3, S. Lu4, V. Georgoulias5, A. Ardizzoni6, S. Gadgeel7, B. Wang8, V.K. Chand9, J. Soria10
  • 1Division Of Medical Oncology, University of Ottawa, K1H 8L6 - Ottawa/CA
  • 2Oncology Department, Vall d`Hebron University Hospital Institut d'Oncologia, Barcelona/ES
  • 3Medical Oncology Department, Hospital Carlos Haya, Malaga/ES
  • 4Shanghai Chest Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai/CN
  • 5Department Of Medical Oncology, University Hospital of Heraklion, Heraklion/GR
  • 6Medical Oncology Department, University Hospital, Parma/IT
  • 7Medical Oncology Department, Karmanos Cancer Institute, Detroit/US
  • 8Biostatistics, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield/US
  • 9Clinical Development Medical Affairs – Oncology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield/US
  • 10Drug Development Department, Gustave Roussy Cancer Campus, Paris/FR



A is an irreversible ErbB family blocker that has shown clinical activity in pts with SCC of the head/neck and lung. This phase III trial prospectively compared A and E in pts with SCC of the lung following failure of platinum-based first-line chemotherapy.


Pts with stage IIIB/IV SCC were randomized 1:1 (stratified by race [East Asian vs other] to avert any possible EGFR mutation imbalance) to receive A (40 mg/day; 50 mg/day from Cycle 2 for pts meeting AE criteria) or E (approved dose of 150 mg/day) until progression. The primary endpoint was PFS by independent radiological review (IRR). Secondary endpoints were OS, ORR, DCR, patient-reported outcomes (PROs) and safety. Between Mar 2012 and Jan 2014, 795 pts were recruited. Primary analysis was based on 414 PFS events when 669 patients had been randomized (A: 335, E: 334) and recruitment ongoing. OS analysis (key secondary endpoint) is planned at 632 deaths. PFS will be updated at that time. An exploratory tumour genomic analysis is also ongoing.


Baseline characteristics were well balanced between arms. Median age was 65y; male 85%; eastern Asian 22%. Median PFS was significantly higher for A than E (2.4 vs 1.9 mths; HR [95% CI]: 0.82 [0.68–1.00]; p = 0.04). Also, ORR (4.8 vs 3.0%; p = 0.23) and DCR (45.7 vs 36.8%; p = 0.02) were higher with A vs E. Overall AE profile was comparable (≥G3 AEs: 50.2 and 49.1%, serious AEs: 39 and 38% for A and E, respectively) with higher incidence of drug-related ≥G3 diarrhoea (9.7 vs 2.4%) and G3 stomatitis (3.3 vs 0%) with A and higher incidence of G3 rash/acne with E (5.5 vs 9.0%). AEs leading to treatment discontinuation were comparable (17.9 vs 13.9%). More patients had improved global health status (36.4 vs 27.1%; p = 0.03) and cough (44 vs 33%; p = 0.01) with A than E. Changes in mean scores over time significantly favoured A vs E for cough, dyspnoea and pain.


LL8 is the largest prospective trial comparing A vs E in pts with relapsed/refractory SCC. PFS and DCR were significantly better for A than E. AEs were comparable and manageable. A was associated with improvements in PROs and symptoms vs E.

Clinical trial identification NCT01523587; October 6 2014


G.D. Goss: Prof. Goss reports; advisory board participation for Boehringer Ingelheim.

E. Felip: Dr. Felip reports; advisory board participation for AstraZeneca and Novartis; and corporate sponsored research for Eli Lilly, Pfizer, Roche and Boehringer Ingelheim.

S. Lu: Prof. Lu reports; advisory board participation for AstraZeneca and Boehringer Ingelheim.

A. Ardizzoni: Andreas Ardizzoni reports; advisory board participation for Boehringer Ingelheim, MSD, Pfizer, BMS, Eli Lilly, GSK, Daiichi Sankyo and Pierre Fabre.

S. Gadgeel: Prof. Gadgeel reports; advisory board participation for Boehringer Ingelheim, Novartis and Genentech.

B. Wang: Dr. Wang reports; employment by Boehringer Ingelheim.

V.K. Chand: Dr. Chand reports; corporate sponsored research (sponsor of Lux-Lung 8 trial) for, and employment by, Boehringer Ingelheim.

J.-C. Soria: Prof. Soria reports; advisory board participation for Boehringer Ingelheim.

All other authors have declared no conflicts of interest.