Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23953

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    P3.02-006 - Monitoring Genetic Alterations in Plasma during Anti-Cancer Treatment in Advanced NSCLC (MAGIC1-Validation Cohort: Preliminary Results) (ID 8927)

    09:30 - 09:30  |  Author(s): G. Pasello
    • Abstract

    Background:
    No molecular markers are available so far to predict the efficacy of treatment and to monitor outcome in patients with EGFR-ALK-ROS1 wild-type advanced non-small cell lung cancer (wtNSCLC). Detection of genetic alterations in plasma may allow to follow biological effects of treatment without invasive procedures. Aim of this study (validation cohort) is to evaluate the detection rate and to monitor tumor-associated mutations in plasma during treatment in wtNSCLC.
    
    Method:
    Advanced wtNSCLCs referring to our Institution and undergoing anti-cancer systemic treatment are prospectively enrolled. Tissue genetic alterations are screened by Sequenom massarray platform (Diatech) or next-generation sequencing (NGS) (Illumina). Plasma samples are collected at baseline, after the first cycle of treatment, at first radiological restaging and at radiological progression. DNA is extracted and analyzed for genetic alterations previously detected in tissue by using droplet digital PCR (ddPCR,Biorad) or real-time PCR (Diatech). Semi-quantitative index of fractional abundancy of mutated allele is used. Primary end-point of MAGIC1 is to assess the sensitivity of technologies to detect genetic alterations in plasma (target: 60% within +/-15%).
    
    Result:
    Since January 2017 we have prospectively enrolled 56 patients treated with platinum-based chemotherapy (28), single-agent chemotherapy (9) or immunotherapy (18). 21 tissue samples have been analyzed (by Sequenom) in order to detect mutations in EGFR, HER2, KRAS, NRAS, BRAF, ALK, MET, PI3K, DDR2: ten KRAS mutation (including 3 G12D, 4 G12C, 2 G13D, 1 G12A mutations), one BRAF V600E and three EGFR exon 20 mutations were detected. At baseline, a concordance plasma/tissue was confirmed in 5/10 KRAS, 0/1 exon 20 EGFR, and 1/1 BRAF mutations. Longitudinal exploratory analysis was performed in 8 patients and 4/5 mutations found at baseline were not detected at subsequent evaluations in patients not experiencing systemic progression. The only patient with persistent KRAS mutation in serial plasma samples experienced radiological progression. In 1/5 patients negative at baseline, one sub-clonal KRAS mutation emerged at the third evaluation when progression was recorded. NGS tissue analysis is ongoing and ddPCR will be used to detect and monitor other genetic alterations such as STK11/LKB1, TP53, AKT mutations. The validation cohort will include 68 patients. MAGIC2 will include an expansion cohort to monitor genetic alterations in plasma during immunotherapy and assess timing of modifications in plasma according to clinical benefit.
    
    Conclusion:
    Preliminary data indicate the feasibility of detecting KRAS and BRAF mutations in plasma in clinical practice and potential usefulness in tracking biological changes in tumors.