Annual Meeting Proceedings Part 1 - American Society of Clinical ...

502s Lung Cancer—Non-small Cell Metastatic
7591 General Poster Session (Board #51A), Sat, 1:15 PM-5:15 PM
EML4-ALK-gene rearrangement comparative analysis in circulating tumor
cells and in tumor tissue of patients with lung adenocarcinoma. Presenting
Author: Marius Ilie, Laboratory of Clinical and Experimental Pathology,
Hospital Pasteur, Academic Hospital, Nice, France
Background: The implementation of new theranostic biomarkers in Oncology
is leading to impressive therapeutic improvements. In patients with
lung cancer, the possibility to use Circulating Tumor Cells (CTCs) as a
non-invasive theranostic approach is a clinically appealing challenge.
Adenocarcinomas with EML4-ALK rearrangement are a new molecular
subgroup of lung tumors with very good response to Crizotinib, an ALK
inhibitor. We have thus aimed at developing an informative assay characterizing
the ALK-gene status in CTCs isolated from patients with lung cancer.
Methods: CTCs were isolated preoperatively using Isolation by Size of
Epithelial Tumor cells method (ISET) from 65 patients with lung adenocarcinoma
and blindly screened for ALK-gene status. ALK break-apart
fluorescence in situ hybridization (FISH) (LSI ALK dual colour probes set)
and immunochemistry using an anti-ALK antibody (5A4 clone) were blindly
performed on CTCs and corresponding tumor tissues and results were
compared. Results: Two patients consistently showed ALK-gene rearrangement
and strong ALK protein expression in CTCs and corresponding tumor
samples. Negative results (both ALK FISH and ALK immunochemistry)
were found in CTCs and corresponding tumor samples from the other 63
patients. Conclusion: We have developed an approach allowing to characterize
ALK-gene status in CTCs from patients with lung cancer and shown
consistent results in CTC and tumor tissues. These preliminary results
encourage larger studies and open new avenues for non-invasive, real-time,
theranostic monitoring of cancer patients.
7593 General Poster Session (Board #51C), Sat, 1:15 PM-5:15 PM
Frequency of anaplastic lymphoma kinase (ALK) positive tumors among
African American non-small cell lung cancer (NSCLC) patients. Presenting
Author: Shirish M. Gadgeel, Karmanos Cancer Institute, Wayne State
University, Detroit, MI
Background: ALK gene rearrangement is a recently identified molecular
alteration in the tumors of a small proportion of NSCLC patients. Previous
reports have shown that the rate of EGFR gene mutations may vary in
NSCLC patients of different ethnic background. It is unclear if similar
differences exist with regards to ALK positivity. We analyzed ALK expression
in tumors of AA NSCLC patients and also assessed the epidemiologic
features and outcomes of these patients, as well as the occurrence of
known oncogene mutations. Methods: We identified 260 tumor tissues of
AA NSCLC patients, enrolled on several epidemiologic studies conducted
at our institution. Immunohistochemistry, using the anti-Alk D5F3 antibody
(Cell Signaling Technology) was used to visualize ALK expression.
Fifty-three of these tumors also underwent mutation analysis using the
OncoCarta Panel V1 (Sequenom) to evaluate 238 mutations in 19
oncogenes. Results: Of the 260 tumors analyzed, 6 (2.3%, 95% CI-
0.5-4.1%) were ALK positive. All ALK positive patients had adenocarcinoma
histology (6/157) while no patients with other NSCLC histologies
were ALK positive, p�0.04. There was no difference in the rate of positivity
based on sex, 1% (1/99) in males versus 3.1% (5/161) in females,
p�0.27. Consistent with prior studies, patients with ALK positive tumors
were slightly younger (median age 56 years vs 61 years, p � 0.27) and the
positive rate was higher in never smokers 11% (2/18) than in ever smokers
1.6%, p�0.06. There was no correlation of ALK positivity with the stage of
the disease at diagnosis. The survival of ALK positive and negative patients,
adjusted for age, sex and stage, was similar (HR�0.77; 95% CI 0.19-
3.13). Fifty-three tumors have been assessed for oncogene mutations in
addition to ALK expression. Of these, 2 (3.8%) were ALK positive and
neither of these tumors carried other tested mutations such as EGFR, Kras,
PIK3 or AKT. Conclusions: The rate of ALK positive tumors among
African-American NSCLC patients is similar to the general population and
the demographic features of ALK positive AA patients is also similar to the
general ALK positive NSCLC patient population.
7592 General Poster Session (Board #51B), Sat, 1:15 PM-5:15 PM
Safety and efficacy analysis by histology of weekly nab-paclitaxel in
combination with carboplatin as first-line therapy in patients (pts) with
advanced non-small cell lung cancer (NSCLC). Presenting Author: Markus
Frederic Renschler, Celgene Corporation, Summit, NJ
Background: Treatment of advanced NSCLC differs by histology, with fewer
options and poorer outcomes in pts with squamous histology. In a phase III
trial of nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles)
� carboplatin (C) vs solvent-based paclitaxel (sb-P) � C, the primary
endpoint of ORR was significantly improved from 25% to 33%, p � 0.005,
with a 1-month improvement in OS (p � NS) and improved safety. This
analysis evaluated efficacy and safety by histology. Methods: Pts with
untreated stage IIIB/IV NSCLC were randomized 1:1 (stratified by age,
histology, region, stage, and gender) to C AUC 6 day 1 and either nab-P 100
mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day1q21days. ORR and PFS
were determined by blinded centralized review. Results: In squamous pts,
nab-P/C produced a significantly higher ORR (41% vs 24%, p � 0.001),
similar PFS (5.6 vs 5.7 mo, HR: 0.865) and �1-month improvement in OS
(10.7 vs 9.5 mo, HR: 0.890) vs sb-P/C (Table). nab-P/C was as effective as
sb-P/C in nonsquamous pts for ORR (26% vs 25%, p � 0.808), PFS (6.9
vs 6.5 mo, HR: 0.933), and OS (13.1 vs 13.0 mo, HR: 0.950). In both
squamous and nonsquamous pts, nab-P/C vs sb-P/C produced lower rates
of grade 3/4 neuropathy (3% vs 11% and 3% vs 12%, respectively, p �
0.001 both), neutropenia (43% vs 51%, p � NS, and 50% vs 63%, p �
0.008), and higher but manageable rates of anemia (27% vs 4% and 28%
vs 9%, p � 0.001 both) and thrombocytopenia (21% vs 7% and 16% vs
11%, p � 0.001 both). Conclusions: In pts with advanced NSCLC, nab-P/C
demonstrated a favorable risk-benefit profile as a first-line therapy regardless
of histology. Significantly improved ORR and a positive trend in OS
were observed in pts with squamous histology.
Squamous
ORR, %
95% CI
Median PFS, mo
95% CI
Median OS, mo
95% CI
Nonsquamous
ORR, %
95% CI
Median PFS, mo
95% CI
Median OS, mo
95% CI
nab-P/C sb-P/C RR/HR P
n � 229
41
35, 47
5.6
5.5, 6.7
10.7
9.4, 12.5
n � 292
26
21, 31
6.9
6.0, 8.1
13.1
11.5, 16.1
n � 221
24
19, 30
5.7
5.4, 6.7
9.5
8.6, 11.6
n � 310
25
20, 30
6.5
5.6, 7.0
13.0
11.1, 14.3
1.680
1.271, 2.221
0.865
0.680, 1.101
0.890
0.719, 1.101
1.304
0.788, 1.358
0.933
0.750, 1.159
0.950
0.779, 1.158
�0.001
0.245
0.284
0.808
0.532
0.611
7594 General Poster Session (Board #51D), Sat, 1:15 PM-5:15 PM
Update on the large-scale screening of ALK fusion oncogene transcripts in
archival NSCLC tumor specimens using multiplexed RT-PCR assays.
Presenting Author: Tianhong Li, University of California, Davis, Sacramento,
CA
Background: The ALK inhibitor crizotinib offers a new standard of care for
advanced NSCLC patients with EML4-ALK fusion oncogenes. We previously
reported a 4.0% frequency of EML4-ALK fusion oncogene transcripts
detected in 1889 NSCLC specimens in the RGI database (Li et al., ASCO
2011). Methods: Patented single and multiplexed RT-PCR assays suitable
for rapid and accurate detection of all variants of ALK fusion oncogene
transcripts were used as previously described, including all 9 known
EML4-ALK fusion gene transcripts and ALK RNA levels (Danenberg, ASCO
2010). The sensitivity and specificity on archival formalin-fixed, paraffinembedded
tumor specimens are 99% and 100%, respectively. We here
update the detection of EML4-ALK fusion transcripts in the RGI database.
Results: Between 12/2009 and 09/2011, 4750 NSCLC specimens in the
RGI database were tested for the presence of ALK fusion transcripts. We
found 152 (3.2%) NSCLC cases with EML4-ALK fusion positivity, including
87 (57.2%) V1, 15 (9.9%) V2, 47 (30.9%) V3, and 3 (2.0%) V5a
variants. Median age (range): 61.1 (33-96). Female: 74 (49%). All
EML4-ALK-positive tumors were adenocarcinomas. No EGFR or K-Ras
mutation was detected in ALK fusion-positive samples. Expression of
chemotherapy-related biomarkers was available from 63 (female: 31,
49%) EML4-ALK-positive cases in the database: 43 (68%) had low TS
level of �2.33; 40 (63.5%) had low ERCC1 level of �1.7, and 25 (40%)
had low RRM1 level of �0.97. Conclusions: This RT-PCR assay provides a
tool for rapid, large-scale screening of NSCLC FFPE tissues for EML4-ALK
fusion gene transcripts. The relative value of this RT-PCR assay as a
companion diagnostic test for drugs targeting ALK merits evaluation in
comparison with the FDA approved ALK FISH test.
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