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

688s Tumor Biology
10630 General Poster Session (Board #53G), Mon, 1:15 PM-5:15 PM
Molecular profiling of uveal melanoma patients. Presenting Author: Zoran
Gatalica, Caris Life Sciences, Phoenix, AZ
Background: Although uveal melanoma represents only 5% of all melanomas,
it is the most common primary intraocular malignancy of the adult
eye. Approximately 50% of patients will develop metastases which are
resistant to medical interventions. There is a great need for improved
therapy as the prognosis is poor for advanced stages. Our study was
undertaken to investigate the presence of novel therapeutic targets.
Methods: We analyzed 49 uveal melanoma patients with immunohistochemistry
for 16 markers including cKIT, PDGFR, cMET, PTEN and IGF1R.
Further, microarray analysis was performed on 29 samples using the
Illumina platform. We also investigated amplification of EGFR and mutational
analysis of cKIT, BRAF, KRAS and NRAS on a smaller patient subset.
Results: Overexpression of KIT at the protein and RNA level was 74% (28
out of 38) and 45% (13 out of 29), respectively. Expression of cKIT did not
correlate with gain-of-function cKIT mutations in any of the 34 samples
tested. In our study, MET was overexpressed in 15 out of 17 cases at the
RNA level and IGF1R was high in 4 out of 6 patients indicating poor
prognosis. PTEN expression by IHC was present in 90% (36 out of 40)
patients indicating the PI3K pathway is not activated in the majority of
uveal melanoma patients. BRAF was wildtype in all 42 patients tested.
Similarly, no KRAS or NRAS mutations were detected. Protein and RNA
expression of PDGFR were low in our patients. MGMT was lost in 16 out of
40 patients at the protein level and 10 out of 29 patients at the RNA level.
EGFR expression, copy number and protein levels were low in the patients
tested. Conclusions: Our data on cKIT suggests that it is a promising target
in uveal melanoma. Low expression of MGMT in about a third of our
patients may indicate the likelihood of favorable response to dacarbazine
and temozolomide. There are currently several clinical trials investigating
various cKIT inhibitors, as well as temozolomide in advanced uveal
melanoma patients. Our findings highlight the importance of molecular
profiling uveal melanoma patients.
TPS10632 General Poster Session (Board #54A), Mon, 1:15 PM-5:15 PM
The PARSC trial, a prospective study for the assessment of recurrence risk
in stage II colon cancer patients using ColoPrint. Presenting Author: Ramon
Salazar, Institut Catala d’Oncologia, Barcelona, Spain
Background: An 18-gene expression profile, ColoPrint, has been developed
for identifying colon cancer patients more likely to develop recurrent
disease and who would be candidates for adjuvant chemotherapy. The gene
signature was validated in public datasets and independent patient cohorts
(stage II and III patients). Uni-and multivariate analysis was performed on
the pooled stage II patient set (n�320) (median follow-up 70 months).
ColoPrint classifies 65% of stage II patients as Low Risk. The 3-year RFS
was 91% for Low Risk and 74% for High Risk patients with a HR of 2.9
(p�0.001). ColoPrint was the only significant prognostic marker in the
subgroup of patients with T3-MSS phenotype (Tabernero, ASCO GI 2012).
Methods: A blinded prospective trial, PARSC (Prospective study for the
Assessment of Recurrence risk in Stage II colon cancer patients) using
ColoPrint has been initiated. Objectives are: (1)To validate the performance
of ColoPrint in estimating the 3-year relapse rate in patients with
stage II colon cancer. (2) To compare the risk assessment in stage II
patients using the ColoPrint profile vs a clinical risk assessment based on
Investigator’s assessment of risk and ASCO high-risk recommendations. (3)
To investigate therapy as a potential confounding factor for ColoPrint
results. (4) To assess the performance of ColoPrint in estimating the 3-year
relapse rate in patients with stage III colon cancer. Inclusion criteria: age �
18 years, adenocarcinoma of the colon, stage II and III, no prior neoadjuvant
therapy, no synchronous tumors, fresh tumor sample, and written
informed consent. The treatment of the patient is at the discretion of the
physician adhering to National Comprehensive Cancer Network (NCCN)approved
regimens or a recognized alternative (blinded for ColoPrint
result). The trial started in Sept. 2008 with currently 32 participating sites
in 11 countries. Thus far, 340 eligible stage II and 280 stage III patients
have been enrolled. The aim is to enroll 575 stage II patients. Clinical trial
registry number: NCT00903565.
TPS10631 General Poster Session (Board #53H), Mon, 1:15 PM-5:15 PM
Detection of discordant HER2 status by FISH in circulating tumor cells and
disseminated tumor cells in early-stage breast cancer using a microfluidicbased
cell enrichment and extraction platform (OncoCEE). Presenting
Author: Savitri Krishnamurthy, University of Texas M. D. Anderson Cancer
Center, Houston, TX
Background: Evaluation of HER2 in circulating (CTCs) and disseminated
(DTC) tumor cells may aid therapy in breast cancer. We report here the
discordance in HER2 status in CTCs and DTCs in early stage breast cancer
by fluorescence in situ hybridization (FISH) using a microfluidic cell
platform (OncoCEE). Methods: Blood (10ml) and BM (1-2ml) from patients
with Stage T1 and T2 breast cancer was collected in OncoCEE-Sure
collection tubes. Mononuclear cells were recovered using a Percoll density
gradient method, incubated with a mixture of 10 primary capture antibodies
(Abs), and introduced into streptavidin coated OncoCEE microchannels
for tumor cell capture. For blood samples, captured cells were stained with
anti cytokeratin (CK) and CD45 Abs for CTC enumeration followed by FISH
using probes specific to centromere 17 and HER2. For BM samples,
captured cells were subjected to HER2 FISH analysis. The ratio of
HER2:CEP17�2.0 in any CK�/ CD45- and CK-/CD45- cell was regarded
as positive for HER2. Results: Blood and BM from 68 patients (68 Blood,
54 BM; 54 matched blood and BM) with stage T1N0 (41), T1N1 (6), T2N0
(11), T2N1(2), T2N2 (1), T2N3 (2) with HER2� (n�7) and HER2-
(n�61) breast cancers were studied. The 7 patients with HER2 � primary
tumor had HER2� DTCs in 3/7 (43 %) and HER2 � CTCs in 1/6 (17 %)
patients. HER2 � DTCs and HER2 � CTCs occurred in 10/47 (21%) and in
4/57 (7%) patients with HER2- primary breast tumors. The discordance of
HER2 status was observed in 14% in CTCs and in 22% in DTCs.
Conclusion: 1. The cell enrichment and extraction microfluidic platform
(OncoCEE) provides a sensitive approach for evaluation of HER2 in CTCs
and DTCs. 2. CTCs and DTCs acquired HER2 gene amplification in 21%
and 7% of patients with HER2 negative early stage primary breast cancer.
3. CTCs and DTCs lost HER2 gene amplified status in 57% and 83% of
patients with HER2 positive early stage primary breast cancer. 4. The
clinical significance of alterations in HER2 status among CTCs and DTCs in
early stage breast cancer needs further investigation.
TPS10633^ General Poster Session (Board #54B), Mon, 1:15 PM-5:15 PM
Emerging findings in the Cancer Research UK stratified medicine program.
Presenting Author: Emily Shaw, Cancer Research UK, London, United
Kingdom
Background: Molecular analysis of tumours may be used to identify those
predicted to benefit from novel targeted therapies. The Cancer Research
UK programme is piloting plans to apply such testing broadly across the UK
healthcare system, linking molecular phenotype to clinical outcomes.
Methods: The Stratified Medicine Programme (SMP) aims to develop a
model for high quality, large-scale molecular characterization of cancer
specimens through an initiative developed in partnership with AstraZeneca,
Pfizer, the UK Department of Health and academic researchers. Phase
One of the SMP is a two year feasibility study. It aims to demonstrate the
submission of consented blood samples and sections of surplus diagnostic
formalin-fixed paraffin-embedded tumour tissue from 9,000 patients at
centres across the UK to one of three ‘technology hubs’ for mutation testing
of genes of potential clinical interest (KRAS, BRAF, NRAS, PIK3CA, TP53,
PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT) in six selected tumour
types. The tests are technically validated and will be completed in clinically
relevant timescales. Data including pathological and treatment information
and clinical outcome is also collected for the recruited patients, linked to
the genetic data and stored in a central data repository hosted within the
National Cancer Registration Service. The study opened in September
2011 at 7 sites across the UK and by the end of 2011, 760 patientswith
breast, lung, prostate, colorectal, ovarian cancer or metastatic malignant
melanoma had consented to participate. 142 sets of molecular results had
been returned to clinical teams. Updated figures will be presented at the
meeting, by which time the programme is projected to have accrued 4000
subjects. By 2013, we hope to have developed a scalable model for routine,
high quality, prospective molecular characterisation of tumours for NHS
cancer patients, with consent for the collection, storage and research use of
population-scale genetic and clinical outcome data. We will report the
emerging results from the Stratified Medicines Programme and early
insights into implications for wider implementation across the UK healthcare
system.
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