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L. Arnold
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P1.06 - Poster Session/ Screening and Early Detection (ID 218)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.06-020 - Detection of Aberrant ALK Expression from Circulating Tumor Cells for Accurate Monitoring of ALK Driven NSCLC (ID 3277)
09:30 - 09:30 | Author(s): L. Arnold
- Abstract
Background:
Insight Genetics Inc. and Biocept, Inc. have established a collaboration to develop a non-invasive work flow to enhance detection of the oncogenic Anaplastic Lymphoma Kinase (ALK) status in NSCLC patients. A barrier to detection of oncogenic transcripts in circulating tumor cells (CTCs) has been purification methods that are incompatible with downstream qPCR detection technologies. In contrast, Biocept's proprietary CTC capture technology has been shown to be benign for follow up qPCR detection using Insight Genetics proprietary qPCR-based oncogenic ALK detection assay.
Methods:
Initial studies were conducted to demonstrate cell capture on the Biocept platform with spiked ALK fusion positive H3122 cells. These studies show this to be a feasible option for non-invasive detection of ALK mRNA. A pre-amplification allele-specific approach including reference controls was incorporated. H3122 cells spiked into peripheral blood also demonstrated feasibility of the accurate detection of aberrant ALK expression using the Biocept CTC extraction methodology and Insight Genetics’ qPCR detection strategy.
Results:
Results from these studies and the detection of aberrant ALK expression from a cohort of ALK positive patients will be presented along with the potential to use CTCs to monitor ALK inhibitor resistant mutation profiles.
Conclusion:
Together, Biocept’s proprietary CTC capture technology coupled to Insight Genetics qPCR ALK detection assay appears to be a viable strategy to accurately monitor ALK status in NSCLC patient populations using a liquid biopsy.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-088 - Surrogate or Not: The Role for Cell Free Circulating DNA in Detecting EGFR Mutations Present in Tumor Tissue (ID 499)
09:30 - 09:30 | Author(s): L. Arnold
- Abstract
Background:
Identification of molecular drivers such as EGFR in non-small cell lung cancer (NSCLC) has increased our capability to deliver personalized cancer therapy. EGFR tyrosine kinase inhibitors (TKI) are very effective in patients with EGFR sensitive mutations, but resistance ultimately develops. Determining mechanisms of secondary resistance requires post progression biopsies which carry non-trivial complication risks for patients and thus are not suitable means for serial monitoring. Cell free circulating DNA (cfcDNA) could represent an alternative method to detect molecular mechanisms of secondary resistance.
Methods:
Single institution observational study of 13 patients with EGFR mutant Stage IV lung adenocarcinoma. Two 8-10 ml tubes of blood were collected from patients who progressed on erlotinib. Patient samples were tested for T790M mutations using the Biocept Selector assay as well as MET using FISH amplification. Results from these “liquid-biopsies” were then compared to results obtained on standard tissue biopsy.
Results:
13 patients with secondary resistance were enrolled, all 13 had adenocarcinoma. Median age was 61 with an age range 52-76, male to female ratio 7:6, 8/13 (62%) had deletion 19, 5/13 (38%) had an L858R mutation. Median duration of EGFR TKI therapy prior to cfcDNA sample collection was 16 months, range 5.2-64.4 months. 9/13 patients underwent a post-progression tissue biopsy with 8/13 found to have the T790M mutation, 1/13 with c-MET amplification, and 1/13 with both. 11/13 patients were found to have T790M in cfcDNA. Average concentration of T790M clone in cfcDNA was 4% with a range from .004-27.6% (from 3mL of blood). Average copy number of T790M in cfcDNA was 2310 with a range from 7-20507 (from 3mL of blood). Average copy number of the EGFR gene in cfcDNA was 39404 with a range from 4308-169628 (from 3mL of blood). Among the 10 patient thus far whose post-progression biopsies and cfcDNA sampling was completed, the sensitivity and positive predictive value (PPV) of Selector was 88% and 88% respectively. Concordance was 80% between cfcDNA and tissue. 7/9 patients with tissue confirmed T790M were switched to third generation TKI with 6/7 currently with stable disease after an average of 7 months (5-9). 1/7 passed away after one month on the next generation TKI due to disease progression.
Conclusion:
Biocept’s blood based assay detecting T790M and MET amplifications from cfcDNA is highly concordant with mutations present in tumor tissue and therefore a non-invasive surrogate for determining mutational status of patients’ who progress on TKI therapy.
