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J. Lim
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-014 - Feasibility of Liquid Biopsy Using Plasma and Platelets for Detection of ALK Rearrangements in Non-Small Cell Lung Cancer (ID 9301)
09:30 - 09:30 | Author(s): J. Lim
- Abstract
Background:
Fluorescence in situ hybridization (FISH) using tissue biopsy specimen is the gold standard for detection and confirmation of ALK rearrangement in non-small cell lung cancers (NSCLC), but it is time-consuming and labor-dependent procedure. Liquid biopsy using reverse-transcriptase polymerase chain reaction (RT-PCR) is expected to overcome these limitations, and provide an easy accessibility and frequent assessment of biomarkers. The aim of this study is to investigate the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement.
Method:
FISH was performed in 664 patients between January 2015 and May 2017. We retrospectively analyzed the formalin-fixed paraffin-embedded (FFPE) tissue and blood sample to detect ALK rearrangement using multiplex RT-PCR from 30 advanced NSCLC patients who had available tissue specimen and agreed with venous sampling. Total RNA were extracted from FFPE cell blocks, plasma and platelets, respectively. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK, the most common translocation, fusion RNA was detected using PANAqPCR[TM] EML4-ALK fusion gene detection kit.
Result:
Twenty-eight patients were FISH positive and two were negative. In a validation data compared with FISH, RT-PCR using FFPE tissue demonstrated 57.1% sensitivity and 69.2% accuracy. Liquid biopsy (plasma or platelets-positive) had higher sensitivity (96.4%) and accuracy (93.3%). Among the specimen of liquid biopsy, platelets showed slightly higher sensitivity and accuracy than plasma (82.1 and 83.3% vs 78.6 and 76.7%). Compared with FFPE tissue using RT-PCR, liquid biopsy showed 100% sensitivity, 20.0% specificity and 69.2% accuracy. Median proportion of positive cells in FISH was higher in subgroups of liquid biopsy with positive result (Plasma, 30.0 vs 15.0%; Platelets 30.0 vs 20.0%), but it was not statistically significant (p=0.062 and 0.104). In 18 patients with crizotinib treatment, platelets-positive subgroup showed a tendency of longer duration of treatment (7.2 vs 1.5 months) and higher response rate (57.1 vs 0.0 %), but the difference was not significant (p=0.071 and 0.100). However, platelets-positive subgroup showed significantly higher disease control rate than platelets-negative subgroup when they were treated with crizotinib (85.7 vs 25.0%, p=0.044).
Conclusion:
Plasma and platelets are a valuable source for liquid biopsy using RT-PCR technique in detection of ALK rearrangement, and they could play a supplementary role in diagnosis of ALK-positive NSCLC. Furthermore, platelets, especially, may be useful for predicting the treatment outcome of crizotinib.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-024 - Phase II Trial of AZD9291 in Second-Line Treatment after Acquired Resistance with T790M Mutation Detected From Circulating Tumor DNA (ID 8736)
09:30 - 09:30 | Author(s): J. Lim
- Abstract
Background:
Administering the best treatment after acquiring resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) requires the knowledge of the resistance status. In this trial, the treatment efficacy of osimertinib (AZD9291) was assessed in patients with non-small-cell lung carcinoma (NSCLC) harboring T790M resistance mutation, which was detected in the circulating tumor DNA (CtDNA) without re-biopsy of the tumor tissue.
Method:
To prove 60% response rate of osimertinib compared to 30% as null hypothesis, and considering 10% drop out rate, 19 subjects were recruited. To extract CtDNA, 15 mL of peripheral blood was withdrawn and centrifuged immediately before storage. Cobas® v2 RUO (Roche diagnostics) and PANA mutyper® (Pangene, Korea) were used to detect the EGFR mutations from CtDNA. Osimertinib was prescribed as an 80 mg tablet once in a day irrespective of the food intake.
Result:
Eighty patients with acquired resistance to prior EGFR TKIs were screened for T790M resistance mutation, and the CtDNA of 21 subjects (26.3%) showed T790M mutation. T790M mutation was detected by both PANA mutyper® and Cobas® in 13 cases, T790M was detected only by PANA mutyper® in 4 cases, and only by Cobas® in 4 cases. Nineteen subjects (age: 64.4 ± 11.6 years old, 14 women, 5 men) were enrolled in this prospective single arm trial from September 2016 to April 2017. Prior EGFR TKIs were afatinib (n=3), erlotinib (n=4), gefitinib (n=10), erlotinib and afatinib (n=1), and gefitinib and afatinib (n=1). Twelve subjects had exon 19 deletion of EGFR gene, 4 had L858R point mutation, one showed exon 19 deletion and L858R, 1 had G719X, and 1 case showed no activating mutation. The response to osimertinib was evaluable in 15 subjects; 4 subjects dropped out from this trial before response evaluation. Among the 15 subjects (efficacy analysis set), partial remission was observed in 10 cases (66.7%).
Conclusion:
Assuming 40% of screened patients are harboring T790M mutation, sensitivity of CtDNA testing is 65% using both tests, and 53% with either test. Toxicity and survival analyses will be followed. (ClinicalTrials.gov Identifier: NCT02769286)
