Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
without PD were included. Overall survival (OS) and progression-free survival
(PFS) were calculated by Kaplan-Meier method. 95% CIs and hazard ratios
estimated using stratified Cox proportional hazards model. Results: Of 1093
patients (ITT population), 982 patients (89.8%) had evaluable IHC assay
results; 935/982 (95.2%) had EGFR>0. GC+N arm continuation therapy
patients included 228 patients with EGFR>0 and 194 patients (EGFR>0) were
GC arm non-progressors. Baseline characteristics were similar except gender
(Males: 81% in GC+N vs 91% in GC arm). CT exposure was balanced. Median OS
from randomization in GC+N vs GC was 16.1 vs 14.9 months; HR 0.76 (95% CI,
0.61, 0.95). Median PFS in GC+N vs GC was 7.4 vs 6.9 months; HR 0.81 (95% CI,
0.66, 1.00).
Conclusion: In patients with EGFR-expressing tumors, a consistent treatment
effect in favor of GC+N continuation maintenance compared to GC nonprogressors
was observed, similar to ITT population with no unexpected
increases in AEs.
Keywords: NSCLC, EGFR, squamous, Necitumumab
Hypothesis-generating analysis of archived tumor samples and blood serum
was undertaken to identify possible molecular/clinical biomarkers. Methods:
Tumor samples were retrospectively analyzed using FoundationOne TM
next-generation sequencing (NGS); EGFR expression was determined by
immunohistochemistry. Pre-treatment serum samples were analyzed with
VeriStrat ® , a MALDI-TOF mass spectrometry test, and classified as VeriStrat-
Good or VeriStrat-Poor-risk. Results: 15/398 patients treated with afatinib
were long-term responders. Median duration of treatment was 16.6 months
(range: 12.3-25.8). Patient characteristics were similar to the overall dataset
(median age: 65 years [range: 54-81]; male: 80.0%; Asian: 13.3%; ECOG 0/1:
40.0%/60.0%; best response to chemotherapy CR or PR/SD: 53.3%/46.7%;
current and ex-smokers: 80.0%). Median PFS was 16.2 months (range:
2.8-24.0); median OS was 23.1 months (range: 12.9-31.5). The most common
treatment-related AEs (all grade/grade 3) were: diarrhea (73.3%/6.7%); rash/
acne (66.7%/6.7%); stomatitis (13%/7%). AEs generally occurred soon after
treatment onset (median onset, days [range]: diarrhea 11 [5-48]; rash/acne
17 [9-107]; stomatitis 15 [11-19]). Four patients required a dose reduction to
30mg/day due to treatment-related AEs (diarrhea, rash, stomatitis, diarrhea/
rash). NGS was undertaken in 9 patients and details will be presented at the
meeting. Genomic aberrations in the ErbB/FGF gene families were identified
in 44.4%/55.6% of long-term responders (overall dataset: 29.4%/58.0%). Of 14
patients assessed by VeriStrat, 85.7% were VeriStrat-Good (overall dataset:
61.6%). Immunohistochemistry data was available for two patients; one
overexpressed EGFR (≥10% positive cells; H-score ≥200) Conclusion: Baseline
characteristics of long-term responders to afatinib were similar to the overall
dataset. In this sub-group, afatinib conferred a survival benefit of nearly 2
years. Afatinib was well tolerated with predictable and transient AEs that
occurred soon after treatment onset. The dataset was too small to identify
any clear NGS/VeriStrat predictive signals. Further studies are required to
predict long-term response to afatinib.
Keywords: afatinib, Squamous cell carcinoma of the lung, NSCLC
OA23: EGFR TARGETED THERAPIES IN ADVANCED NSCLC
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
OA23: EGFR TARGETED THERAPIES IN ADVANCED NSCLC
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
OA23.03 SECOND-LINE AFATINIB FOR ADVANCED SQUAMOUS CELL
CARCINOMA OF THE LUNG: ANALYSIS OF AFATINIB LONG-TERM
RESPONDERS IN THE PHASE III LUX-LUNG 8 TRIAL
Glenwood Goss 1 , Manuel Cobo 2 , Shun Lu 3 , Kostas Syrigos 4 , Alessandro
Morabito 5 , Istvan Albert 6 , Gabriella Herodek 7 , Samuel Chan 8 , Gyula Ostoros 9 ,
Veronika Sarosi 10 , Zsolt Kiraly 11 , Deric Savior 12 , Rachael Barton 13 , Francisco
Medina 14 , Sundaram Subramanian 15 , Andrea Ardizzoni 16 , Enriqueta Felip 17 ,
Shirish Gadgeel 18 , Vassilis Georgoulias 19 , James Love 20 , Claudia Bühnemann 21 ,
Neil Gibson 22 , Eva Ehrnrooth 23 , Jean-Charles Soria 24 , Nicholas Dupuis 25
1 Division of Medical Oncology, University of Ottawa, Ottawa/ON/Canada,
2 Department of Medical Oncology, Hospital Carlos Haya, Malaga/Spain, 3 Shanghai
Chest Hospital Affiliated To Shanghai Jiao Tong University School of Medicine,
Shanghai/China, 4 Athens School of Medicine, Athens/Greece, 5 Medical Oncology
Unit, Thoracic Department, Istituto Nazionale Tumori “Fondazione G.Pascale”-
IRCCS, Naples/Italy, 6 Mátrai Gyógyintézet, Mátraháza/Hungary, 7 Aladar Petz
County Teaching Hospital, Györ/Hungary, 8 Harrogate and District NHS Foundation
Trust, Harrogate/United Kingdom, 9 Department of Pulmonology, Semmelweis
University, Budapest/Hungary, 10 Department of Respiratory Medicine, Medical
University, Pécs/Hungary, 11 Veszprem County Lung Hospital, Farkasgyepü/
Hungary, 12 Temple University Cancer Center, Philadelphia/PA/United States of
America, 13 Scarborough District General Hospital, Scarborough/United Kingdom,
14 Oca Hospital, Monterrey International Research Center, Monterrey/Mexico,
15 V.S. Hospitals, Chennai/India, 16 University Hospital, Bologna/Italy, 17 Vall D’
Hebron University Hospital, Barcelona/Spain, 18 Karmanos Cancer Institute/wayne
State University, Detroit/MI/United States of America, 19 University Hospital of
Heraklion, Heraklion/Greece, 20 Boehringer Ingelheim Corporation, Ridgefield/CO/
United States of America, 21 Boehringer Ingelheim Pharma Gmbh & Co., Kg Biberach/
Germany, 22 Boehringer Ingelheim Pharma Gmbh & Co., Biberach/Germany,
23 Boehringer Ingelheim, Danmark A/s, Copenhagen/Denmark, 24 Department of
Medicine, Gustave Roussy Cancer Campus and University Paris-Sud, Paris/France,
25 Biodesix Inc., Boulder/CO/United States of America
Background: Squamous cell carcinoma (SCC) of the lung is a genetically
complex and difficult-to-treat cancer. In LUX-Lung 8, afatinib (40mg/day)
significantly improved OS (median 7.9 vs 6.8 months, HR=0.81 [95% CI, 0.69-
0.95], p=0.008), PFS (2.6 vs 1.9 months, HR=0.81 [0.69-0.96], p=0.010) and DCR
versus erlotinib (150mg/day) in patients with relapsed/refractory SCC of the
lung (n=795). Notably, 12-month (36 vs 28%; p=0.016) and 18-month survival
(22 vs 14%; p=0.016) was significantly higher with afatinib than erlotinib,
indicating that some patients derive prolonged benefit from afatinib.
Here, we present post-hoc analysis of baseline characteristics and efficacy/
safety of afatinib in long-term responders (treatment for ≥12 months).
OA23.05 FIRST-LINE AFATINIB VERSUS GEFITINIB IN EGFRM+
ADVANCED NSCLC: UPDATED OVERALL SURVIVAL ANALYSIS OF
LUX-LUNG 7
Keunchil Park 1 , Eng Huat Tan 2 , Li Zhang 3 , Vera Hirsh 4 , Ken O’Byrne 5 , Michael
Boyer 6 , James Chih-Hsin Yang 7 , Tony Mok 8 , Ki Hyeong Lee 9 , Shun Lu 10 , Yuankai
Shi 11 , Sang-We Kim 12 , Janessa Laskin 13 , Dong-Wan Kim 14 , Scott Laurie 15 , Karl
Kölbeck 16 , Jean Fan 17 , Nigel Dodd 18 , Angela Märten 19 , Luis Paz-Ares 20
1 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/
Korea, Republic of, 2 Medical Oncology, National Cancer Centre, Singapore,
Singapore/Singapore, 3 State Key Laboratory of Oncology in South China,
Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University,
Guangzhou/China, 4 McGill University, Montreal/QC/Canada, 5 Princess Alexandra
Hospital and Queensland University of Technology, Brisbane/QLD/Australia, 6 Chris
O’Brien Lifehouse, Camperdown/NSW/Australia, 7 National Taiwan University
Hospital and National Taiwan University Cancer Center, Taipei/Taiwan, 8 Key
Laboratory of South China, the Chinese University of Hong Kong, Hong Kong/
China, 9 Chungbuk National University Hospital, Cheongju, Chungbuk/Korea,
Republic of, 10 Shanghai Chest Hospital, Shanghai/China, 11 National Cancer Center,
Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical
College; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted
Drugs, Beijing/China, 12 Asan Medical Center, Seoul/Korea, Republic of, 13 BC Cancer
Agency, Vancouver/BC/Canada, 14 Seoul National University Hospital, Seoul/Korea,
Republic of, 15 The Ottawa Hospital Cancer Centre, Ottawa/ON/Canada, 16 Karolinska
University Hospital, Solna, Stockholm/Sweden, 17 Boehringer Ingelheim
Pharmaceuticals, Inc., Ridgefield/CT/United States of America, 18 Boehringer
Ingelheim Ltd Uk, Bracknell/United Kingdom, 19 Boehringer Ingelheim Pharma
Gmbh & Co. Kg, Ingelheim Am Rhein/Germany, 20 Hospital Universitario Doce de
Octubre and Cnio, Madrid/Spain
Background: The irreversible ErbB family blocker afatinib and the reversible
EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+
NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib
in this setting. Methods: LUX-Lung 7 assessed afatinib (40 mg/day) versus
gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC
harbouring a common EGFR mutation (Del19/L858R). Co-primary endpoints
were PFS (independent review), time to treatment failure (TTF) and OS. Other
endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drugrelated
AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum).
The primary analysis of PFS/TTF was undertaken after ~250 PFS events.
The primary OS analysis was planned after ~213 OS events and a follow-up
period of ≥32 months. Results: 319 patients were randomised (afatinib: 160;
gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57-
0.95], p=0.017), TTF (0.73 [0.58-0.92], p=0.007) and ORR (70 vs 56%, p=0.008)
were significantly improved with afatinib versus gefitinib. The most common
grade ≥3 AEs were diarrhoea (13%) and rash/acne (9%) with afatinib and
elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib
had ≥1 dose reduction due to AEs; dose reductions were more common in
S170 Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017