Download the ESMO 2012 Abstract Book - Oxford Journals

abstracts
non-small cell lung cancer, metastatic
1225O A RANDOMIZED PHASE 2 STUDY OF ERLOTINIB PLUS
PEMETREXED VS ERLOTINIB OR PEMETREXED ALONE AS
SECOND-LINE TREATMENT FOR NEVER-SMOKER
PATIENTS WITH NON-SQUAMOUS ADVANCED NON-SMALL
CELL LUNG CANCER (NSCLC)
D.H. Lee 1 , J.S. Lee 1 , S.W. Kim 1 , J. Rodrigues Pereira 2 , B. Han 3 , X.Q. Song 4 ,
J. Wang 5 , H-K. Kim 6 , T. P. Sahoo 7 , R. Digumarti 8 , X. Wang 9 , S. Altug 10 ,
M. Orlando 11
1 Asan Medical Center, Seoul, KOREA, 2 Grupo de Assistencia Médica, Sao
Paulo, BRAZIL, 3 Shanghai Chest Hospital, Shanghai, CHINA, 4 Affiliated Cancer
Hospital of Guangxi Medical University, Nan Ning, CHINA, 5 Beijing Tumor
Hospital, Beijing, CHINA, 6 St. Vincent Hospital, Suwon, KOREA, 7 Chirayu
Medical College and Hospital, Bhopal, INDIA, 8 Nizam’s Institute of Medical
Sciences, Hyderabad, INDIA, 9 Eli Lilly and Company, Shanghai, CHINA, 10 Eli Lilly
and Company, Istanbul, TURKEY, 11 Eli Lilly and Company, Buenos Aires,
ARGENTINA
Background: Erlotinib (E) and Pemetrexed (P) are approved second-line treatments
in patients (pts) with relapsed NSCLC and may be effective in combination. This
randomized phase 2 study compared the efficacy and safety of E + P vs either agent
alone, as second-line treatment in never-smoker pts with advanced non-squamous
NSCLC.
Methods: From Nov 2007 to Jul 2010, never-smoker NSCLC, ECOG Performance
Status (PS) ≤2 pts who had failed 1 prior chemotherapy regimen were enrolled
and randomized to either: E 150 mg daily, P 500 mg/m 2 day 1, or P 500 mg/m 2
day 1 plus E 150 mg daily on days 2 to 14 of a 21-day cycle, continued until
discontinuation criteria were met. The primary endpoint of progression-free
survival (PFS) was analyzed using a sequential approach. A multivariate Cox
model was used to perform a global comparison across the 3 arms with pairwise
comparisons between treatments using contrasts within the model. If the global
null hypothesis was rejected at a 2-sided 0.2 significance level (SL), then 2
pairwise comparisons of E + P vs E or P were conducted. Statistical significance
was claimed if both pairwise and global null hypotheses were rejected at a
2-sided 0.05 SL.
Results: A total of 240 non-squamous pts (Male, 34.6%; East Asian, 55.4%; ECOG
PS 0-1, 92.9%) were included. A statistically significant difference in PFS was found
across the 3 arms (global p = 0.003), with E + P significantly better than both single
agents (HR (95% CI) for E + P vs E was 0.57 (0.40, 0.81), p = 0.002; for E + P vs P
was 0.58 (0.39, 0.85), p = 0.005). Median PFS (95% CI) was 7.4 months (4.4, 12.9) in
E + P, 3.8 (2.7, 6.3) in E and 4.4 (3.0, 6.0) in P. Safety analyses showed a higher
number of pts with ≥1 TEAE with CTCAE grade 3/4 toxicity in E + P (n = 45;
60.0%) than in P (n = 10; 28.9%) or E (n = 22; 12.0%), the majority being
neutropenia, anemia, rash and diarrhea.
Conclusions: Erlotinib + Pemetrexed significantly improved PFS compared to either
agent alone in this clinically selected population. E + P had more toxicity, but was
clinically manageable. Further analysis of the EGFR mutational status will help to
understand and predict which pts will benefit most from this approach.
Disclosure: X. Wang: I am employee of Eli Lilly and Company. S. Altug: I am
employee of, and hold stock/stock options in, Eli Lilly and Company. M. Orlando: “I
Annals of Oncology 23 (Supplement 9): ix400–ix446, 2012
doi:10.1093/annonc/mds409
am employed by and hold stock in Eli Lilly & Company”. All other authors have
declared no conflicts of interest.
1226O BIOMARKER ANALYSES AND OVERALL SURVIVAL (OS)
FROM THE RANDOMIZED, PLACEBO-CONTROLLED, PHASE
3, FASTACT-2 STUDY OF INTERCALATED ERLOTINIB WITH
FIRST-LINE CHEMOTHERAPY IN ADVANCED
NON-SMALL-CELL LUNG CANCER (NSCLC)
T.S.K. Mok 1 , J.S. Lee 2 , L. Zhang 3 ,C.Yu 4 , S. Thongprasert 5 , G.E.I. Ladrera 6 ,
V. Srimuninnimit 7 , M.I. Truman 8 , B. Klughammer 9 ,Y.Wu 10
1 Department of Clinical Oncology, Chinese University of Hong Kong, Prince of
Wales Hospital, Hong Kong, HONG KONG, 2 Research Institute and Hospital,
National Cancer Center, Goyang, KOREA, DEMOCRATIC PEOPLE’S REPUBLIC
OF, 3 Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou,
CHINA, 4 Department of Internal Medicine, National Taiwan University Hospital,
Taipei, TAIWAN, 5 Faculty of Medicine, Chiang Mai University, Chiang Mai,
THAILAND, 6 Department of Pulmonary Medicine, Lung Center of the Philippines,
Quezon City, PHILIPPINES, 7 Department of Medicine, Siriraj Hospital, Mahidol
University, Bangkok, THAILAND, 8 Department of Biometrics, F. Hoffmann-La
Roche Ltd., Sydney, AUSTRALIA, 9 Pharmaceutical Division, F. Hoffmann-La
Roche Ltd., Basel, SWITZERLAND, 10 Guangdong Lung Cancer Institute,
Guangdong General Hospital & Guangdong Academy of Medical Sciences,
Guangzhou, CHINA
Background: FASTACT-2 is a randomized, placebo-controlled, phase 3 study in
first-line advanced NSCLC, which met its primary endpoint of significantly
prolonged PFS with intercalated erlotinib and chemotherapy: median 7.6 vs 6.0
months; HR = 0.57; p < 0.0001 (Mok et al. ASCO 2012). We report OS results and
correlations of biomarkers with PFS for this study.
Methods: Patients (pts) with untreated stage IIIB/IV NSCLC and ECOG PS 0/1
received up to 6 cycles of gemcitabine (1,250 mg/m 2 on d1 & 8) plus platinum
(carboplatin AUC = 5 or cisplatin 75 mg/m 2 on d1) q4w, with either intercalated
erlotinib (150 mg/day on d15–28; GC-E; n = 226) or placebo (GC-P; n = 225). Pts
without progression received maintenance erlotinib or placebo until progression,
unacceptable toxicity or death. Provision of tumour samples was encouraged;
tests were conducted at a central laboratory and prioritized as follows: EGFR
mutation; KRAS mutation (both by PCR-based test [COBAS]); ERCC1 expression
by immunohistochemistry (IHC; median cut-off); EGFR gene copy number by
fluorescence in-situ hybridization (FISH); and EGFR IHC.
Results: OS data are not fully mature yet (45.1% and 52.4% of pts in GC-E and
GC-P arms with event, respectively, in Oct 2011), but a trend towards prolonged OS
with GC-E vs GC-P was observed: HR = 0.78 (95% CI 0.60–1.02); p = 0.0686; median
18.3 vs 14.9 months. Updated OS data with June 2012 cut-off will be presented. A
total of 283/451 pts (62.7%) provided samples for biomarker analyses. The table
shows correlations with PFS for the overall biomarker populations and the EGFR
wild-type (WT) subgroup.
Conclusions: As expected, the EGFR mutation-positive (Mut+) subgroup had the
strongest PFS benefit with intercalated erlotinib and first-line chemotherapy. ERCC1
IHC+ status was also associated with longer PFS with GC-E vs GC-P, even in pts
with known EGFR WT status.
© European Society for Medical Oncology 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oup.com