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Marie Florescu



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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-19 - Treatment Cessation for Improved Detection of EGFR-Mutated Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer (aNSCLC) (ID 11329)

      16:45 - 18:00  |  Author(s): Marie Florescu

      • Abstract
      • Slides

      Background

      First/second generation EGFR-tyrosine kinase inhibitors (EGFR-TKI) are eventually met with therapeutic failure in EGFR-mutated (EGFRm) aNSCLC, but post-progression continuation of therapy can delay the need for second line therapy by a median of ~ 3 months. In this context, osimertinib was shown to be effective in T790M mutated EGFR, which occurs in > 50% of cases. T790M detection within circulating tumor DNA (ctDNA) is convenient but has suboptimal sensitivity. The goal of this study is to determine whether temporary cessation of the TKI - beyond initial progression - would allow for increased plasma detection of EGFR mutations.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      EGFRm aNSCLC patients who were still on first/second generation EGFR-TKI beyond initial progression were enrolled. TKI was withheld on day 0. Blood samples were drawn and the NCCN-FACT FLSI-17 questionnaire v2 was administered on days 0 and 6±1. Semi quantitative measurements of EGFR mutations within plasma samples were obtained using the cobas® EGFR Mutation Test v2. Descriptive statistics were reported and paired t-test was used to compare differences in ctDNA yield and quality of life after TKI cessation.

      4c3880bb027f159e801041b1021e88e8 Result

      33 patients were enrolled in 2017. Baseline characteristics and relevant study results are summarized in Table 1. Temporary TKI cessation was safe with no tumor flares reported - questionnaire scores indicate a trend towards improved quality of life one week after TKI cessation. The yield of detection was significantly higher after TKI cessation, but only for the baseline sensitizing mutation.

      Table 1
      Age, Median - years (range) 71(46 - 87)
      Gender, female n (%) 25 (75.8)
      Median time to progression on first/second generation TKI, months (range) 9.76 (0.3 - 46)
      Median time from initial progression to study enrollment, months (range) 1.03 (0.25 - 7.57)
      NCCN-FACT FLSI-17 questionnaire
      - Questionnaire score day 1
      - Questionnaire Score day 6/7

      - 45.81±10.78
      - 48.41±9.91 (p=0.08)
      Baseline EGFR sensitizing mutation
      - Overall detection of ctDNA, n (%)
      - Detection within ctDNA on only one of the two test dates, n (%)

      Semi quantitative index of detected ctDNA
      - Day 1
      - Day 6/7

      - 21 (63.6)
      - 6 (28.5)


      - 5.2±6.2
      - 6.1±6.4 (p=0.04)
      T790M EGFR mutation
      - Overall detection of ctDNA, n (%)
      - Detection within ctDNA on only one of the two test dates, n (%)

      Semi quantitative index of detected ctDNA
      - Day 1
      - Day 6/7

      - 21 (63.6)
      - 6 (28.5)


      - 5.2±6.2
      - 6.1±6.4 (p=0.04)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data suggest that TKI cessation can lead to increased shedding of ctDNA in sensitive cells. However, drug withdrawal may not impact the shedding of ctDNA in resistant clones. Irrespective of drug withdrawal, a strategy of repeat testing appears to increase the sensitivity of ctDNA detection and would likely produce more clinically relevant outcomes in comparison with one-time testing.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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