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1262P DISTINCT SPREAD OF EGFR MUTATED PULMONARY
ADENOCARCINOMAS
D. Shin 1 , S.Y. Kwon 2 , C.H. Kim 1 , S.H. Yang 1 , I.I. Na 1
1 Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological
and Medical Sciences, Seoul, KOREA, 2 Hospice and Palliative Care Team, Korea
Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences,
Seoul, KOREA
Introduction: Our aim in this study was to explore the potential association of
epidermal growth factor receptor (EGFR) with characteristics of tumor spread in
patients with pulmonary adenocarcinoma. Clinical implication of EGFR mutational
status on brain metastasis was also evaluated in surgically treated patients.
Methods: We analyzed clinical data on 317 patients who were tested for EGFR
mutation and who underwent brain MRI at diagnosis between October 2005 and
December 2011. The relationship between EGFR mutation status and clinical factors
were analyzed. Initial metastatic disease was stratified according to brain metastases
and their association with EGFR mutations was evaluated using multinomial logistic
regression.
Results: Of the 317 patients, 139 patients (43.85%) harbored EGFR mutations. EGFR
mutations was more commonly found in patients with early nodal stage (71.9 %
versus 28.1%, adjusted odds ratio [OR] = 1.90, p = 0.030) and distant metastases
(54.0% versus 46.0%, adjusted OR = 2.05, p = 0.011). Further analysis showed that
EGFR mutations were more likely to be detected in brain metastases (64.7% versus
35.3%, p = 0.005), whereas their association with noncranial metastases was not
significant (55.4% versus 44.6%, p = 0.960). In addition, survival analysis of 133
patients treated with surgical resection showed that EGFR mutation status was a poor
prognostic factor for brain metastasis (HR = 5.94, 95% CI = 1.08-16.28, p = 0.039)
after adjustment of pathologic N stage.
Conclusions: In this study, EGFR mutation status was significantly associated with
early nodal and distant metastasis, in the patients with pulmonary adenocarcinoma.
The current study also suggests the preference of brain metastases in mutant EGFR
tumors at initial presentation and after curative resection.
Disclosure: All authors have declared no conflicts of interest.
1263P IMPACT OF EPIDERMAL GROWTH FACTOR
RECEPTOR-TYROSINE KINASE INHIBITOR TREATMENT IN
ADVANCED NON-SMALL CELL LUNG CANCER: A
META-ANALYSIS
C.K. Lee 1 , C. Brown 2 , R. Gralla 3 , V. Hirsh 4 , A. Inoue 5 , V. Gebski 6 , C.J. Yang 7
1 NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, AUSTRALIA,
2 Clinical Trials, NHMRC Clinical Trials Centre, University of Sydney, Sydney,
AUSTRALIA, 3 Department of Medicine, Hofstra University School of Medicine,
New York, UNITED STATES OF AMERICA, 4 Oncology, McGill University Health
Centre, Montreal, QC, CANADA, 5 Department of Respiratory Medicine, Tohoku
University, Sendai, JAPAN, 6 Biostatistics and Research Methodology, NHMRC
Clinical Trials Centre, University of Sydney, Sydney, AUSTRALIA, 7 Department of
Oncology, National Taiwan University Hospital, Taipei, TAIWAN
Background: Previous meta-analyses have reported that epidermal growth factor
receptor (EGFR)-tyrosine kinase inhibitor (TKI) improves progression-free
survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC)
harbouring EGFR mutation. We examined the influence of EGFR-TKI on PFS
and overall survival (OS) in those with (EGFR+) and without mutation
(EGFR-).
Methods: We included published and unpublished randomised trials of advanced
NSCLC that compared EGFR-TKI monotherapy or combination EGFR-TKI
chemotherapy with chemotherapy or placebo. We used published hazard ratios (HR)
if available, or derived treatment estimates from other survival data. We investigated
treatment effects in different treatment settings and trial regimens.
Results: We identified 20 eligible trials investigating EGFR-TKI in front-line (n = 12),
second or subsequent (n = 5), and maintenance (n = 3) treatment, with EGFR status
known in 3198 (23%) patients. Overall, HR for EGFR-TKI over control for PFS were
(EGFR+) 0.37 (95% CI, 0.32 to 0.42; p < 0.001) and (EGFR-) 1.02 (95% CI, 0.93 to
1.12; p = 0.67). EGFR mutation is predictive of PFS benefit with EGFR-TKI in all
settings: front-line HR (EGFR+) 0.39, p < 0.005, HR (EGFR-) 1.07, p = 0.27,
interaction p < 0.001; second or subsequent lines HR (EGFR+) 0.38, p = 0.01, HR
(EGFR-) 1.22, p = 0.07, interaction P = 0.003; maintenance HR (EGFR+) 0.15, p <
0.001, HR (EGFR-) 0.81, p = 0.02, interaction p = 0.02. There was no difference in OS
for patients treated with EGFR-TKI or control in these subgroups of patients: HR
(EGFR+) 0.95, p = 0.21; HR (EGFR-) 0.95; p = 0.29.
Conclusions: In this meta-analysis, treatment with EGFR-TKI was found to
significantly delay disease progression in EGFR+ patients; however, no impact on
OS was identified. EGFR mutation is a predictive biomarker of PFS benefit
with EGFR-TKI treatment in all settings. These findings support assessment for
Annals of Oncology
EGFR mutation before initiation of EGFR-TKI treatment and that EGFR-TKI
should be considered as front-line therapy in EGFR+ patients with advanced
NSCLC.
Disclosure: R. Gralla: Consultant or advisory role for Boehringer Ingelheim. V.
Hirsh: Advisory role for Boehringer Ingelheim. A. Inoue: Received lecture fees and
research grants from AstraZeneca. C.J. Yang: Advisory roles for Boehringer
Ingelheim, AstraZeneca, Roche and OSI, and have received honoraria from
AstraZeneca, Roche and OSI. All other authors have declared no conflicts of
interest.
1264P CLINICOPATHOLOGIC FEATURES OF NEVER-SMOKING
WOMEN LUNG CANCER (WLC): A REVIEW FROM THE
SPANISH WORLD07 DATABASE
J. De Castro 1 , D. Isla Casado 2 , M. Provencio Pulla 3 , M. Majem Tarruella 4 ,
N. Vinolas Segarra 5 , E. Felip 6 , A. Artal-Cortes 7 , R. García-Campelo 8 ,
M. Domine 9 , P. Garrido Lopez 10
1 Medical Oncology, Hospital Universitario La Paz, Madrid, SPAIN, 2 Oncology
Service, Hospital Clínico Universitario Lozano Blesa, Zaragoza, SPAIN, 3 Medical
Oncology, Hospital Universitario Puerta de Hierro Majadahond, Majadahonda,
SPAIN, 4 Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona,
SPAIN, 5 Medical Oncology, Hospital Clinic y Provincial de Barcelona, Barcelona,
SPAIN, 6 Oncologia Médica, Vall d’Hebron University Hospital Institut
d’Oncologia, Barcelona, SPAIN, 7 Servicio de Oncologia Medica, Hospital Miguel
Servet, Zaragoza, SPAIN, 8 Medical Oncology, Complexo Hospitalario
Universitario de A Coruña, La Coruña, SPAIN, 9 Oncology, Fundación Jiménez
Díaz, Madrid, SPAIN, 10 Medical Oncology, Hospital Ramon y Cajal, Madrid,
SPAIN
Background: Lung cancer in never-smoker appears to be a distinct entity from lung
cancer in smoker, with specific molecular characteristics and potential different
treatment. Several factors like hormonal, environmental, genetic, pre-existing lung
diseases, and virus, may play etiologic roles, and an in-depth understanding of them
is needed. So, new clinicopathologic aspects of never-smoking WLC should be very
important to know the biology of this tumoral disease.
Methods: Information has been extracted from WORLD07 database, a prospective,
from 32 Spanish centers, epidemiologic female-specific lung cancer e-database
performed by ICAPEM, an association to research WLC.
Results: From October 2007 to October 2011, 539 newly diagnosed never-smoking
WLC were included in World07 database (39.3% of 1371 patients(p). P
characteristics are: median age 71.1 years(y) (range: 22-91). Previous history of
cancer (%): 13(breast, lung, cervix: 41.4,5.7,2.9). Gynecological features: median age
of menarche 13y, Postmenopausal 88.9%, median age of menopause 49y. Median age
of first child 26.4y Children: 91.2% (median: 2.3). Oral contraceptive: 11.9%. HRT:
5.2%. Tobacco exposure: Second-hand smokers: 40%, work-exposure 17.1%,
home-exposure 88.8%. Obesity: 16.3%. Familiar history of cancer: 39.9% (lung cancer
29.8%).Lung cancer histology (%): adenocarcinoma/BAC/squamous/large cell/SCLC/
others: 69.2/6.8/5.7/5.0/3.8/3.8. EGFR mutated p (268 p analized): 55.5%, exon 19/
20/21(%): 61.1/7.4/36.9. TNM NSCLC I/II/III/IV (%): 14/3.3/19.8/60.3. Treatment:
EGFR-TKI in p harboring EGFR mutations stage IV (1 st -/2 nd -line)(%): 51.7/15.4;
stage IV NSCLC(1 st -line)(%): platinum-based chemotherapy 42.5, combinations with
bevacizumab 2.9. Overall survival: median 27 months (m), 1/2-y(%) 74.8/55.2; stage
IV NSCLC: median 20.5m, 1/2-y(%) 67/46; EGFR mutated p: median 27.3m, 1/2-y
(%) 75/54.3.
Conclusions: Never-smoking WLC represents 39% of Spanish World07 database.
The high incidence of adenocarcinoma histology (69.2%) and EGFR mutated tumors
suggests a different clinical and genetic profiling and recommend a different
treatment approach for this group of patients.
Disclosure: All authors have declared no conflicts of interest.
1265P IS THERE A BENEFIT ON SURVIVAL OF TYROSINE-KINASE
INHIBITORS VERSUS CHEMOTHERAPY IN FIRST LINE IN
MUTATED EGFR PATIENTS WITH ADVANCED NON-SMALL
CELL CANCER (NSCLC)? A META-ANALYSIS
G. Des Guetz 1 , B. Uzzan 2 , K. Chouahnia 1 , P. Nicolas 2 , L. Zelek 1 , M. Pailler 1 ,
J. Morère 1
1 Oncology, Hôpital Avicenne, Bobigny, FRANCE, 2 Pharmacology, Hôpital
Avicenne, Bobigny, FRANCE
Background: Tyrosine-Kinase Inhibitors (TKIs) markedly improve Progression
Free Survival (PFS) of advanced NSCLC patients mutated for Epidermal Growth
Factor Receptor (EGFR). Results on Overall Survival (OS) are more questionable.
Therefore, we performed a publication-based meta-analysis to further assess this
issue.
ix414 | Abstracts Volume 23 | Supplement 9 | September 2012