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stage IIIA NSCLC, EML4-ALK fusion-positive patients had poorer DFS than those
EML4-ALK fusion-negative patients (P = 0.0057). Moreover, multivariate Cox
proportional hazard analysis indicated that in stage IIIA NSCLC EML4-ALK fusion
was the only significant predictor for poor DFS (HR = 4.4, 95% CI 2.0-9.7, P < 0.001).
We further found that ERCC1 was highly expressed in EML4-ALK fusion-positive
tumors.
Conclusion: Oncogenic driver mutations define molecular subsets of Chinese
NSCLC patients with distinct clinicopathological characteristics. EML4-ALK fusion
might be a significant prognostic biomarker for locally advanced stage NSCLC.
Disclosure: All authors have declared no conflicts of interest.
1194P TISSUE AND SERUM BIOMARKER RESULTS FROM THE
PHASE II INNOVATIONS STUDY IN NON-SMALL CELL LUNG
CANCER (NSCLC)
N. Reinmuth 1 , S.J. Scherer 2 , R. Penzel 3 , P. Schnabel 4 , M. Meister 1 ,
J. Kiemle-Kallee 5 , A. Reuss 6 , J.R. Fischer 7 , M. Wolf 8 , M. Thomas 1
1 Department of Thoracic Oncology, Thoraxklinik Heidelberg, University of
Heidelberg, Heidelberg, GERMANY, 2 Pharma Development Department,
F. Hoffmann-La Roche Ltd/Genentech, San Francisco, CA, UNITED STATES OF
AMERICA, 3 Institute of Pathology, University of Heidelberg, Heidelberg,
GERMANY, 4 Department of Pathology, University of Heidelberg, Section for
Thoracic Pathology, Heidelberg, GERMANY, 5 Pharma AG, Roch Pharma AG,
Grenzach, GERMANY, 6 Coordinating Center for Clinical Trials, Phillips-University
Marburg, Marburg, GERMANY, 7 Department of Medical Oncology, Klinik
Löwenstein, Löwenstein, GERMANY, 8 Division of Haematology and Oncology,
Klinikum Kassel, Kassel, GERMANY
Background: The phase II INNOVATIONS study was a randomised trial of 224
patients (pts) with advanced non-squamous NSCLC who received 1 st -line treatment
with either erlotinib (E) plus bevacizumab (B) or cisplatin (P) plus gemcitabine (G)
plus B. PGB was superior to EB for progression-free survival (PFS). Pts with EGFR
mutation-positive NSCLC were most likely to benefit from EB [1]. This abstract
reports exploratory analyses from the optional biomarker (BM) sub-study for a
number of candidate BMs commonly examined in previous NSCLC bevacizumab
trials.
Methods: Tissue (t) markers were determined by immunohistochemistry H-score.
Serum (s) markers were analysed on day 0 and 43 using a novel protein array/ELISA.
Median baseline values were used to dichotomise pts (low vs high BM) and to
correlate BMs with PFS/overall survival (OS) (Cox model). Analyses were not
adjusted for multiple testing.
Results: BM population represented 88% of the intent-to-treat population; baseline
characteristics were well balanced. Tissue (n = 198) and serum samples (day 0, n =
184; day 43, n = 151) were provided for BM analysis. Soluble VEGFA was not
assessed; only serum samples were available. Serum analyses: PFS was longer for the
BM population with low baseline IL8 and FLT4 (HR = 0.55, p < 0.05 and HR = 0.50,
p < 0.05, respectively); the trend was consistent in EB and PGB treatment arms.
Similar results were seen for day 43 analyses (PFS/OS). Low baseline FLT1 was
associated with longer PFS in PGB pts (HR = 0.53, p < 0.05). Low ICAM levels were
associated with better clinical outcomes (PGB arm). Tissue analyses: None of the
three tumour markers tested showed significant association with PFS/OS (p > 0.05).
Significant correlations (p < 0.05) were observed between tumour and serum
markers: tVEGFR1 and tVEGFR2/tVEGF; tVEGFR2 and tVEGF; sFLT1 and sTie2;
sKDR and sICAM; sFLT4 and sICAM.
Conclusion: Several serum baseline candidate BMs showed a statistically significant
correlation with OS/PFS, in particular FLT4/IL8. The choice of treatment partner
(E/PG) for bevacizumab may influence the value of BMs. Further examination of the
data from this and other bevacizumab trials may provide greater insight. [1] Thomas
et al. J Clin Oncol 2011;29:7504
Disclosure: N. Reinmuth: Advisory Board, Lilly Corporate sponsored research, F.
Hoffmann-La Roche Ltd. S.J. Scherer: Currently employed by Roche/Genentech. J.
Kiemle-Kallee: Currently employed by Roche. M. Thomas: Attended advisory boards
for Roche and Lilly. Received research funding from Roche and Lilly. All other
authors have declared no conflicts of interest.
1195P DETECTION OF ANAPLASTIC LYMPHOMA KINASE (ALK)
GENE REARRANGEMENT IN NON-SMALL CELL LUNG
CANCER (NSCLC): A GLANCE AT “BORDERLINE” CASES
M. von Laffert 1 , E. Berg 1 , D. Lenze 1 , P. Lohneis 1 , M. Hummel 1 , M. Dietel 2
1 Institue of Pathology Charité, Charite Berlin Mitte, Berlin, GERMANY, 2 Surgical
Pathology, Charité, Humboldt-Universität zu Berlin, Berlin, GERMANY
Background: Lung cancer is the leading cause of cancer related mortality in men
and women. In ∼5% [range: 0.9-13] of NSCLC a genomic EML4-ALK fusion has
been described, showing therapeutically sensitivity for ALK-inhibitors. Although
much has been reported about clinical and histological data of this NSCLC subtype
(young patients, non-smokers, solid/mucinous adenocarcinomas), the parameters for
Annals of Oncology
FISH-based (e.g. threshold of positive cells, signal distance) diagnosis vary among the
different studies.
Material and methods: We performed retrospective screening (tissue microarray
based) of 488 NSCLC (336 adenocarcinomas, 152 squamous cell carcinomas) for
ALK-expression (IHC-intensity: 0-3) using immunohistochemistry (Novocastra) and
ALK-breaks using FISH (Abbott, ALK break-apart with positivity if split signals or
single red signals were detectable in ≥15% per 100 cells). The evaluation of the IHC
and FISH data was performed independent from each other. Since various thresholds
for ALK-break positivity have been reported in the literature, special attention was
given to cases with ALK-breaks in the range of 12%-20%.
Results: 95.7% (467/488) of the cases were ALK-break-negative (