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M.G. Dal Bello
MINI 34 - RNA and miRNA (ID 162)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
MINI34.03 - Novel microRNA Prognostic Signature in Malignant Pleural Mesothelioma (ID 2988)
18:30 - 20:00 | Author(s): M.G. Dal Bello
Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure. MPM patients have a poor outcome (median overall survival (mOS) <1 year), therefore novel therapeutic approaches are needed. MiRNA have been demonstrated to have a role in tumorigenesis and progression in MPM. This study aimed to identify a miRNA signature associated with poor prognosis.
We identified 26 un-resected MPM patients split as follows: 11 long survivors (LS) OS>3 years and 15 short survivors (SS) OS<1 year. MiRNA expression in 26 FFPE biopsy and 3 normal pleura (NP) was evaluated using Agilent Human miRNA Microarray platform including 2006 miRNA. Expression data were normalized by GeneSpring software (v.12.6). Class-comparison analysis between MPM/NP and SS/LS was performed using a t-test adjusted for multiple comparisons using Benjamini-Hochberg. OS curves were estimated using the Kaplan-Meier method and compared with the log-rank test. In silico validation was performed using miRseq data from TCGA portal based upon 16 patients (LS: 8; SS: 8). Candidate miRNA were assessed by univariate analysis using Kaplan-Meier method and median as cutoff.
Patients’ characteristics: median age 67 years (53-77); 81% males, 19% females; 73% epithelioid histotype, 12% sarcomatoid, 12% biphasic and 1 unspecified MPM. No differences in age, gender and histotype were observed between LS and SS. By class-comparison analysis, 30 miRNAs were significantly up-regulated and 11 down-regulated in MPM vs NP (adjusted p-value <0.05). Fourteen miRNAs were significantly associated with outcome, in the univariate survival analysis and differentially expressed in MPM. A miRNA signature, based on the top 6 prognostic miRNAs (unfavorable, miR-1224; favorable, miR-99a, miR-125b, let-7b, let-7c and let-7i) classified patients into low- or high-risk. High-risk patients showed a significantly shorter median OS (4.1 months, 95% CI 2.2-5.9) as compared with low-risk patients (median not reached, Log-rank p<0.001). In silico validation analysis confirmed that low expression of mir-99a, miR-125b and let-7c was associated with shorter OS. Relevant pathways, such as PI3K/AKT, WNT were associated with these top miRNAs by pathway analysis.
A prognostic miRNA signature was identified by profiling a cohort of un-resected MPM, underlying the clinical potential of miRNA as predictors of survival. An additional validation in a larger independent cohort of MPM is ongoing.
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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)
P2.01-057 - Serum Mass-Spectrometry Test in First-Line Advanced Non-Small Cell Lung Cancer Patients Treated with Standard Chemotherapy Regimens (ID 2309)
09:30 - 17:00 | Author(s): M.G. Dal Bello
The mass-spectrometry based serum test VeriStrat® (VS) was developed using samples from non-small cell lung cancer (NSCLC) patients (pts) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs); VS was shown to be prognostic in several tumors and predictive of differential overall survival (OS) benefit for erlotinib vs. chemotherapy (CT) in 2[nd] line for NSCLC. We investigated the role of VS in pts receiving Cisplatin (CDDP) or Carboplatin (CBDCA) plus Pemetrexed (P) as 1[st] line for advanced, non-squamous NSCLC.
VeriStrat classification was available for 55 eligible pts, who were classified as VS Good (VSG) or VS Poor (VSP); VS testing was done blinded to clinical data. Progression-free survival (PFS) and OS were analyzed by Kaplan-Meier method and compared using log-rank p-values; Cox models were used in multivariate analysis. Association with categorical variables was analyzed by Fisher’s exact test.
36 (65%) pts were classified as VSG and 19 (35%) as VSP. In the overall population, median PFS was 6.1 months (mo) for VSG vs.1.3 mo for VSP (hazard ratio (HR) 0.39 [0.21-0.70], p=0.001 ); adjusted HR (AHR) 0.43 [0.21-0.91], p=0.026). Median OS was 10.6 mo for VSG vs. 3.1 mo for VSP (HR 0.26 [0.14-0.50], p<0.001; AHR 0.20 [0.09-0.47], p<0.001). A similar relationship was found in both treatments: In CBDCA-P median PFS in VSG and VSP was 3.9 mo and 1.6 mo respectively (HR 0.34 [0.14-0.81], p=0.011); median OS was 10.0 mo in VSG and 2.0 mo in VSP (HR 0.26 [0.11-0.61], p=0.001). In CDDP-P median PFS was 6.6 mo in VSG and 1.2 mo in VSP (HR 0.52 [0.20-1.33], p=0.161), median OS was 12.3 mo in VSG, 3.5 mo in VSP (HR 0.25 [0.09-0.70], p=0.005).When compared within VS groups, no statistically significant differences between CBDCA-P and CDDP-P was found either for PFS (VSG: p=0.471, VSP: p=0.493) or OS (VSG: p=0.319, VSP: p=0.429). VS was significantly associated with disease control rate (p=0.003) and objective response (p=0.021).
Population (N°) Median PFS (months) Hazard ratio, p Median OS (months) Hazard ratio, p VSG VSP VSG VSP Overall (55) 6.1 1.3 0.39 [0.21-0.70] p=0.001 10.6 3.1 0.26 [0.14-0.50] p<0.001 CBDCA-P (30) 3.9 1.6 0.34 [0.14-0.84] p=0.011 10.0 2.0 0.26 [0.11-0.61] p=0.001 CDDP-P (25) 6.6 1.2 0.52 [0.20-1.33] p=0.161 12.3 3.5 0.25 [0.09-0.70] p=0.005
VeriStrat has prognostic significance in platinum-based CT: overall, VSP pts have significantly shorter PFS and OS than VSG pts. In each VS group, CDDP-P and CBDCA-P showed similar behavior. Further research is needed to find alternative treatments to improve outcomes for VSP pts. ClinicalTrials.gov Identifier: NCT02055144.