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Robert Kieszko

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    P3.13 - Targeted Therapy (Not CME Accredited Session) (ID 979)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.13-08 - Assessment of EGFR Gene Mutations In cf-DNA in Monitoring of Response to EGFR TKIs in Patients with Lung Adenocarcinoma (ID 12474)

      12:00 - 13:30  |  Author(s): Robert Kieszko

      • Abstract
      • Slides


      Molecular analysis of cf-DNA in NSCLC patients enables detection and monitoring of EGFR mutations. It allows for detection of the acquired resistance for 1st and 2nd generation of EGFR-TKIs caused Thr790Met substitution. The third generation of EGFR-TKIs (osimertinib) could overcome the resistance in patients with Thr790Met mutation.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The studied group included 23 Caucasian patients (8 male and 15 female, median age 71±9) with diagnosed lung adenocarcinoma and with EGFR mutations detected in tumor samples. Blood samples were collected before administration of EGFR-TKIs in all patients, and re-collected repeatedly from 10 patients during therapy. EGFR mutations and content of mutated cf-DNA were analyzed using ctEGFR Mutation Analysis Kit (Entrogen, USA) in Rotor-Gene Real-Time PCR device (Qiagen, Germany).

      4c3880bb027f159e801041b1021e88e8 Result

      Analysis of EGFR activating mutations in cf-DNA showed 82.61% concordance/sensitivity (19/23) with tumor samples. The mean content of mutated cf-DNA was 7.44% and it was significantly lower (p<0.000035) than in tumor samples (34.54%). Concentration of mutated cf-DNA positively correlated with advanced stage of the disease. Monitoring of EGFR status in cf-DNA showed reduction and stabilization of mutant DNA content with the emergence of response to EGFR-TKIs treatment. Primary Thr790Met substitution was undetectable in cf-DNA and in tumor samples. Acquired resistance in Thr790Met mechanism during EGFR-TKIs treatment was detected only in one patient (1/10). This patient responded to osimertinib therapy.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Analysis of EGFR mutations in cf-DNA shows lower sensitivity than in DNA isolated from tumor samples. Multiple evaluations of EGFR status may be useful in monitoring of therapy and allows for early detection of acquired resistance.


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