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MINI 34 - RNA and miRNA (ID 162)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
MINI34.06 - MicroRNA 10b, 27a and 27b Are Upregulated in Lung Cancer Cell with Epidermal Growth Factor (EGFR) Mutation Resistant to EGFR TKI (ID 2950)
18:30 - 20:00 | Author(s): C.H. Huang
EGFR Tyrosine Kinase Inhibitor (TKI) is now standard of care in lung cancer patients with EGFR mutation. Invariably, these patients develop resistance and would require treatment with another EGFR TKI or chemotherapy. The gate keeper mutation T790M is responsible for about 50% of resistance cases. There are other mechanisms that could confer resistance in these patients. High expression of microRNA (mir) 10 is associated with worse prognosis in resected lung cancer patients with EGFR mutation. The mir 27a and 27b is associated with increased expression of c-met which is a potential mechanism of resistance to EGFR. We explored the expression of mir 10b and 27a and 27b in lung cancer cell lines with EGFR mutation that were resistant to Erlotinib.
Lung cancer cell lines with EGFR mutation CRL-2868 and CRL 2871 were treated with 5 nM of erlotinib for 24hours and 72 hours. The erlotinib resistant cells were then harvested and then microRNA profiling was done by real time PCR. HTB177 cell line without EGFR mutation was used as control.
We observed an increased expression of mir 10b, mir27a and mir27b in CRL-2871 compared to control HTB 177 cells. Mir 27b is upregulated in both cell lines. The increase expression of mir 10b and mir 27a were higher in CRL-2871 than the control cells 9 fold and 8 folds respectively. The mir 27b was increased 300 folds in the CRL 2868 compared with control.
We observed upregulation of mir 10b, 27a and 27b in lung cancer cells lines with EGFR mutation that were resistant to Erlotinib treatment. This suggests an epigenetic mechanism of resistance other than the T790M mutation. Further research in patients with EGFR mutation resistance to EGFR TKI should be done to confirm this finding.
P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
P2.01-069 - Design and Stratification for Phase III Trials in First-Line Non-Small Cell Lung Cancer (ID 80)
09:30 - 17:00 | Author(s): C.H. Huang
Metastatic non-small cell lung cancer (NSCLC) remains an incurable disease. Sacher et al reviewed phase III studies in first-line advanced/metastatic NSCLC conducted from 1981 to 2010. Although trends in study outcomes were assessed, design and stratification factors have never been analyzed.
The recently published list of phase III trials by Sacher et al (JCO 2014;32:1407-11) was reviewed thoroughly. Eligible trials for this study must have been published in the English literature between 1981 and 2010. Trials that included a substantial number of previously treated NSCLC patients were excluded. Maintenance studies after first-line chemotherapy were also excluded. Characteristics in each decade were determined for sample size, number of trials, region, rate of meeting accrual goal, primary endpoint, type of phase III, interim analysis, allocation method, and stratification factors (SFs). Any p-value of less than 0.05 was considered significant for statistical analysis.
A total of 162 studies were considered to meet the criteria. The number of studies and median sample size increased from 29 and 133 in 1980s to 46 and 181 in 1990s to 87 and 407 in 2000s, respectively. Primary endpoint was reported more frequently in recent decades; 24% of studies in 1980s, 83% in 1990s, 99% in 2000s. Non-overall survival endpoints were frequently chosen in European and Asian studies. Interim analysis was planned for 3% in 1980s, 20% in 1990s, 33% in 2000s. Allocation method was rarely reported throughout the three decades (0% in 1980s, 22% in 1990s, 28% in 2000s). The median number of SFs increased significantly from one in 1980s to three in 2000s (see Table). Performance status (PS), stage, and institution have been most frequently selected, and at least one of the three factors was used in most of the studies (84%) in 2000s. There are many other SFs that were used infrequently. More details will be presented. Table: SFs in first-line phase III NSCLC trials. All others; stratification factors other than PS, stage, and institution. The median number of SFs increased significantly (one way ANOVA, p=0.003).
1981-1990 1991-2000 2001-2010 Total No. of studies 29 46 87 162 Median no. of SFs 1 2 3 2 PS 14(48%) 21(46) 48(55) 83(51) Stage 2(7) 22(48) 63(72) 86(53) Institution 2(7) 17(37) 37(43) 56(35) PS or Stage 15(52) 29(63) 6(7) 113(70) PS, Stage, or Institution 16(55) 32(70) 73(84) 121(75) Not reported or None 12(41) 13(28) 13(15) 38(23) All others 1(3) 1(2) 1(1) 3(2)
This study reports extensive details in design of phase III trials for first-line NSCLC that have been published over three decades. We found increases in sample size and reporting primary endpoint, whereas allocation method remains underreported. Although PS, stage, and institution are the most frequently selected, choice of SFs remains inconsistent across studies. Our report provides researchers with valuable information for future studies.
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