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K. Nakatomi
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-069 - Phase II Trial of Paclitaxel, Irinotecan, and Bevacizumab for Patients with Untreated NSCLC Overexpressed ERCC1 MRNA; Evaluated by EBUS-GS (ID 1362)
09:30 - 09:30 | Author(s): K. Nakatomi
- Abstract
Background:
We prospectively evaluated the efficacy and toxicity of non-platinum triplet regimen, which consist of paclitaxel, irinotecan, and bevacizumab for patients with advanced non-small cell lung cancer (NSCLC) expected to be platinum resistant.
Methods:
All patients were diagnosed with NSCLC using endobronchial ultrasonography with a guide sheath (EBUS-GS) system. We defined the EBUS-GS as a core biopsy. RNA was immediately isolated from this unfixed biopsy specimens, and quantitative real-time reverse transcriptase PCR assays were performed to determine the excision repair cross-complementing 1 (ERCC1) mRNA expression. Patients with advanced, untreated NSCLC showing high ERCC1 levels (ΔCt≧6.5) were entered the phase II trial of the non-platinum triplet regimen. Paclitaxel of 180mg/m2 on day 1, irinotecan of 50mg/m2 on day 1 and 8, and bevacizumab of 15mg/kg on day 1 were administered every 4 weeks. Primary end point was the objective response rate (ORR), assuming 30% for a standard therapy and 60% for a target therapy (alpha=0.05 and beta=0.1), and the estimated required total number of patients was 28 by Simon’s Optimal Two-stage Design.
Results:
Total 141 untreated patients received EBUS-GS and were evaluated the expression of ERCC1, and 30 patients were entered in this trial. The ORR was 66.7%(95% confidence interval [CI]: 47.2-82.7). Median progression-free survival was 174 days. Grade 4 thrombosis occurred one patient, but other toxicities were mild and controllable. Fifty-three patients were treated with platinum-containing regimens and 22 patients were responded (ORR was 41.5% [95% CI: 28.1-55.9]). Twenty-three of these patients were high ERCC1 levels and 6 patients were responded, and 30 patients were low ERCC1 levels and 16 patients were responded (p=0.0053, by Fisher’s exact test).
Conclusion:
The triplet combination of paclitaxel, irinotecan and bevacizumab might be effective for patients with advanced, untreated NSCLC overexpressing ERCC1. ERCC1 mRNA levels extracted from unfixed lung biopsy specimens obtained by EBUS-GS also might be a predictive factor for platinum-containing regimens.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-008 - Detection of EML4-ALK Fusion Gene by Using Nested Long-Ranged Polymerase Chain Reaction (ID 704)
09:30 - 09:30 | Author(s): K. Nakatomi
- Abstract
Background:
The fusion of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein-like 4 (EML4) was identified in Non-small cell lung cancer (NSCLC). ALK tyrosine kinase inhibitors were proved to be superior to standard chemotherapies and it is important to detect EML4-ALK fusion gene accurately. Reverse transcriptase-polymerase chain reaction (RT-PCR), Fluorescence in situ hybridization (FISH) and Immunohistochemical (IHC) stain are performed clinically to detect the fusion gene. However, there are discrepancies among these methods for detection of EML4-ALK fusion gene and the best detection method remain unknown. The purpose of this study was to evaluate the new method for detection of the EML4-ALK fusion gene.
Methods:
The combination of nested polymerase chain reaction (PCR) and ｌong-ranged PCR (Nested long-ranged PCR) was used to detect EML4-ALK fusion gene. Genomic deoxyribonucleic acid (gDNA) was extracted from EML4-ALK positive lung cancer cell lines (NCI-H2228,NCI-H3122,ALKSFA8). It was verified whether the fusion gene was amplified. We evaluated the sensitivity of Nested long-ranged PCR for EML4-ALK fusion gene in various ratios. It was confirmed whether the amplification products were EML4-ALK fusion gene by using PCR direct Sequencing.
Results:
EML4-ALK fusion genes were detectable successfully in each of EML4-ALK positive lung cancer cell lines.NCI-H3122 had EML4-ALK variant 1. ALK-SFA8 and NCI-H2228 had EML4-ALK variant 3a/b. One fusion gene in the presence of 1×10[2] wild type genes was detectable in each cell line. Each PCR product was confirmed by sequencing from both ends.
Conclusion:
In this study, we were able to detect the fusion gene in vitro by Nested long-ranged PCR. This may become a new diagnostic method for EML4-ALK fusion gene.
