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A. Catino



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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-038 - Comparison of expression profiling of circulating and tissue miRNAs looking for possible non-invasive biomarkers for the treatment of metastatic NSCLC patients: preliminary results. (ID 2787)

      09:30 - 09:30  |  Author(s): A. Catino

      • Abstract

      Background
      Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Although some progress has been made in the development of its treatment, most patients are diagnosed at advanced stage and have a short overall survival rate. Just as specific genes have to be analyzed before selecting a targeted therapy, microRNAs (miRNAs) are emerging as biomarkers for NSCLC diagnosis and prognosis. miRNAs are small oligonucleotides that regulate target mRNAs in the post-transcriptional step driving the expression of some genes involved in the tumorigenesis of NSCLC. Due to their resistance to nuclease digestion, miRNAs can be detected both in lung tissue samples and in body fluids as circulating factors. Our aim was to identify specific non-invasive cancer biomarkers involved in NSCLC tumorigenesis regulation.

      Methods
      33 NSCLC patients, 19 male and 14 female, were enrolled. The mean age was 63.3 and 66% were smokers. 88% of patients had advanced stage (IIIb-IV) tumors of which 23 were adenocarcinoma and 10 squamous cell carcinoma. We collected serum before chemotherapy and, when available, tissue samples from biopsy. MiRNA expression profiling of 33 serum and 10 tissue paired samples and 10 serum samples from normal volunteers were investigated by Affymetrix GeneChip miRNA Array. meV software was used for statistical analysis, and target genes identified by deregulated miRNAs were analyzed through the miRWalk database.

      Results
      Statistical analysis revealed 47 miRNAs differentially expressed in NSCLC serum samples compared to control serum (p<0.05) and 29 miRNAs deregulated in NSCLC tissue samples compared to their normal counterparts. 326 miRNAs resulted differentially expressed between the serum and the tissue of NSCLC patients. Among these deregulated miRNAs, the Venn diagram comparing tumor/normal serum, tumor/normal tissue and tumor serum/tissue samples showed that the serum of NSCLC patients was characterized by 22 miRNAs, while 10 miRNAs identified the tumor tissue of NSCLC patients. Only one miRNA, miR-133a, was detected both in NSCLC serum samples and in tissue ones. Focusing on miRNAs involved in NSCLC pathogenesis, of 22 miRNAs miR-486-5p had a lower mean expression ratio (MER) in tumor vs normal serum (8.70±3.28 vs 10.78±1.35), as did let7b which had a MER of 5.28±2.63 in tumor serum vs 7.14±1.8 in normal serum samples. Of 10 miRNAs, miR-200c had the lowest MER in tumor vs normal tissue (1.25±0.10 vs 2.37±0.09 respectively) as did miR-29c* which had a MER of 2.18±0.08 in tumor tissue samples vs 2.34±0.11 in normal tissues. miR-133a had a comparable MER in tumor serum vs tumor tissue (2.41±0.17 vs 2.46±0.17 respectively). These miRNAs are able to target PIK3CA and PTEN genes, according to the miRWalk database, which are involved in the EGFR-related pathway.

      Conclusion
      Our results highlighted specific miRNA expression profiles, both in the serum and in the tissue of NSCLC patients, able to identify circulating miRNAs that could be used as non-invasive biomarkers for early diagnosis, or to predict prognosis in NSCLC patients thus improving personalized therapy. These data are preliminary to a prospective clinical validation in a multicentric trial.

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-007 - First-line Pemetrexed plus Cisplatin followed by maintenance Pemetrexed vs Carboplatin-Paclitaxel plus Bevacizumab followed by maintenance Bevacizumab (ERACLE) in advanced non squamous non-small Cell Lung Cancer : a Quality of Life-oriented, multicenter randomized phase III trial of the GOIM (Gruppo Oncologico Italia Meridionale). (ID 749)

      09:30 - 09:30  |  Author(s): A. Catino

      • Abstract

      Background
      Chemotherapy (CT) for advanced non-squamous non-small cell lung cancer (NS-NSCLC) without oncogenic drivers remains palliative with suggested similar efficacy and survival among different regimens. Histotype, maintenance therapy (m) and quality of life (QoL) have been explored to improve patients (pts) outcome. The ERACLE trial (NCT01303926), a QoL-oriented phase III trial, was designed to compare the QoL for two CT regimens.

      Methods
      Pts with stage IIIB/IV NS-NSCLC (ECOG 0/1) were randomized (1:1) to receive first-line CT. Arm A received 6 cycles of Cisplatin (C) (75 mg/m[2])/Pemetrexed (P) (500 mg/m[2]) q3w, followed by mP (500 mg/m[2]), while Arm B received Carboplatin (Cb) AUC 6/Paclitaxel (T) 200 mg/m[2] plus Bevacizumab (Be) 15 mg/kg q3w for 6 cycles, followed by mBe 15 mg/kg. Both treatments were administered until progression, unacceptable toxicity or death. Stratification was based on Study Centre and disease stage. Co-Primary endpoints were EQ5D Index (EQ5D-I) and EQ5D-VAS (Euro-QoL questionnaire). Quality of life data were collected at three time points during the induction phase and at 12 and 18 weeks during the maintenance phase. Secondary endpoints were QoL over time, safety and activity of CT arms. A sample size of 49 pts per arm (that have not progressed during initial CT and during maintenance therapy for at least 12 weeks) would have 91% chance to have 12-point Minimal Interesting Difference (MID) between arms for EQ5D-VAS, and 87% chance to find 0.137 MID between arms for EQ5D-I. It is assumed that about 20% of pts in both arms experience progressive disease before the evaluation of the primary endpoint. The study sample was then increased to 118.

      Results
      From 1/2011 to 3/2012, 118 pts were randomized to Arm A (n=60) or Arm B (n=58). Baseline demographics were well balanced across arms; Arm A/Arm B male: 70%/77.6%, PS 0: 78.3%/79.3%, stage IV 95%/93%, smokers: 63%/52% . Seventy four pts (62,7%) received maintenance chemotherapy. Treatment differences (mean change from baseline), EQ5D-VAS = 1.82 (95%CI -8.60 to 12.24; P=0.73), EQ5D-I = 0.15 (95%CI 0.01 to 0.29), favoured arm A. Safety was as expected without relevant haematological toxicity and with a significant impact of G3/4 alopecia (p=0.002) and G 1-3 neurotoxicity in ARM B (p=0.008) during induction. Response rates were (Arm A/Arm B) partial responses 40%/51%; stable disease 48.3%/27.6%. The Hazard Ratio (HR) for Progression Free Survival Arm A/Arm B [Cox's analysis] was 0.62 (95%CI 0.41 to 0.95) p=0.03 and HR for Overall Survival Arm A/Arm B [Cox's analysis] was 0.69 (95%CI 0.61 to 1.04) p=0.08.

      Conclusion
      Arm A showed better (over the MID) health profile (EQ5D-I) as compared to Arm B. EQ5D-VAS didn’t find any significant difference between treatment arms. By assuming equal activity, the choice of a treatment for advanced NSCLC should be mainly based on QoL.