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J. Adam



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    O27 - Clinical Trials and Practice (ID 142)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Other Topics
    • Presentations: 1
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      O27.07 - Molecular multidisciplinary tumor board (MMTB) for lung cancer patients: 2-year experience report (ID 2865)

      17:20 - 17:30  |  Author(s): J. Adam

      • Abstract
      • Presentation
      • Slides

      Background
      Molecular analysis (MoA) of non-small cell lung cancer has led to definition of many subgroups that require dedicated treatments, strategy and trials. We created a monthly MMTB dedicated to lung cancer patients (pts) with potential driving molecular abnormalitie(s). MMTB includes physicians from the lung tumor board and the phase I unit, pathologists and biologists. A medical report summarizes the findings and treatment recommendations. We report 2 years of activity of MMTB.

      Methods
      All consecutive files discussed in MMTB in Gustave Roussy were reviewed. Tumor and pts characteristics were collected as well as treatment. Pts outcome was calculated from the MMTB.

      Results
      245 pt files were discussed between February 2010 and March 2012. 53% were male, 27% never-smokers, 89% had PS 0 or 1, median age was 59. Clinical initial stage was III-IV in 17 pts (7%) and 78%/11%/11% were adenocarcinoma/squamous cell carcinomas/others NSCLC. Time from diagnosis to MMTB was 7 months (m) (1-222), 102 (42%) of pts received more than 1 line of treatment before MMTB. Biopsy for MoA mostly came from CT guided biopsies (61%), surgery (22%) or endoscopy (15%). Biopsy was repeated in 20% of pts to get enough material for MoA. The MoA results were ALK rearrangement in 10%, exon 18/19/21 EGFR mutation (mut) in 2/14/8%, KRAS mut in 30%, PI3KCA mut in 0.4%, BRAF mut in 3%, HER2 mut in 1%, FGFR1 amplification in 3%, other rare mutations in 14%. MMTB recommendations were: a clinical trial in 75 pts (31%), receive an EMA-approved drug in 49 pts (20%), an off-label commercial drug in 18 pts (7%), an expanded access program in 18 pts (7%), none in 85 pts (35%). Out of the 160 MMTB pts with treatment recommendations, 63 (42%) received the proposed targeted therapy and 16 (11%) might receive it at the time of disease progression. After MMTB, 84 pts (34%) received 1 line, 66 pts (27%) 2 lines or more, 56 pts (23%) no treatment (unknown in 39 pts). Median follow-up is 20.6 m. Progression-free (in 224 pts) and overall survivals (OS, in 221 pts) from MMTB are 3.5 and 13.4 m. In univariate analysis for OS, the pts who received the recommended treatment from the MMTB had a better prognosis (hazard ratio [HR]: 0.56, p=0.002), confirmed in multivariate analysis (HR=0.61 [95% confidence interval: 0.42-0.88], p=0.009) after taking into account histology, previous platinum-based treatment and the number of previous treatment lines.

      Conclusion
      MMTB leads to treatment recommendations in a majority of the pts, fosters inclusion in clinical trials or expanded access programs, and limits the use of off labelled drugs. Updated data will be presented

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    P3.18 - Poster Session 3 - Pathology (ID 177)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P3.18-018 - Results of upfront genomic testing in non-small cell lung cancer (NSCLC) patients (MSN study) (ID 3066)

      09:30 - 09:30  |  Author(s): J. Adam

      • Abstract

      Background
      Recent advances in lung cancer have identified potential driver mutations that may be targeted. On the basis of routine screening for EGFR we have initiated a comprehensive large-scale sequencing analysis of genes potentially mutated in NSCLC.

      Methods
      Genomic DNA was extracted prospectively from untreated advanced NSCLC tumors. All materiel was obtained IRB-approved protocols and after patients’ consent (MSN trial "Melanoma – Small-cell lung cancer – Non-small cell lung cancer "). Pathology specimens were macrodissected, after DNA extraction, 106 selected exons from 38 genes were analyzed by Sanger sequencing (EGFR, KRAS, HER2,4, BRAF, PI3KCA, PIK3R1, TP53, CDK4, CDKN2A, cKIT, PDGFRA, MET, FGFR2-4, FCGR2A,3A, FLT3, CTNNB1, GNAS, HRAS, NRAS, KDR, PDPK1, TOP1,2A, ERCC1, FBXW7, TSC2, PTEN, AKT1-3, MAP2K1-2, STK11, ALK). ALK rearrangements and HER2 amplification were detected by FISH. All result therapeutic outcomes were discussed monthly in a molecular thoracic multidisciplinary staff.

      Results
      Thus far (between May 2009 and September 2012), 351 patients (pts) have been included. The median age was 60 years (range 22-87), 212 (60%) were male, 248 (71%) had adenocarcinoma, 286 (81%) were former/current smokers. A complete failure of the analysis was observed in 78 (22%) pts mostly due to insufficient tumor cells in the specimen (<30%) or poor quality DNA. EGFR, KRAS, HER2, BRAF, PI3CA and ALK (“standard biomarkers”), analysis were performed in 235 (67%), 233 (66%), 207(59%), 221(63%), 139 (40%) and 206 (59%) pts respectively. Depending of markers, success rate was between 77% and 86 % (failures include scarce tumor sample). Two hundred and sixty three pts had at least one result for the EGFR, KRAS or ALK, and 176 pts had all three. 107 pts had a whole genomic analysis and 244 had at least one (1-6 biomarkers) standard biomarkers analysis. Ten (3.8%) pts had concurrent oncogenic mutation. The molecular profiles were characterized by 16% EGFR, 26% KRAS, 1% HER2, 0.8% PI3KCA mutated, 7% HER2 amplification and 11% ALK rearrangement. The pts with the while genomic analysis had 12 other genes evaluated for more than 80 pts and 13 pts had mutation (STK11, PDPK1, PTEN, NRAS, MET, KDR, FGFR4, HER4). A personalized targeted therapy was proposed in most of pts with a genomic alteration. Median OS of pts with at least one mutation/translocation for EGFR, KRAS, BRAF or ALK (n=152) was 13 and 17 months (p=0.006) in wild type or mutated pts respectively. In univariate analysis for OS (median follow-up: 19 months), KRAS mutated pts had a poor prognosis (hazard ratio [HR]=1.56, p=0.037), confirmed in multivariate analysis (HR= 1.78, p=0.008), EGFR mutated pts had a good prognosis (HR=0.48, p=0.01), BRAF and ALK mutations/translocation had no prognostic value.

      Conclusion
      Routine mutational profiling of advanced NSCLC is feasible in the vast majority of the pts but an extensive molecular portrait can be performed only in a limited number of pts. The molecular profile may have an impact on pts treatment strategy at our cancer institute. KRAS mutation is associated with poor prognosis. Updated results will be presented.