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  P1.03 - Biology (Not CME Accredited Session) (ID 935)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26432

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    P1.03-34 - Combined Molecular and Radiological Evaluation Unveils Three Subtypes of Disease Progression to a Third Generation EGFR TKI (ID 12055)

    16:45 - 18:00  |  Author(s): Han Zhang-Han
    • Abstract
    • Slides

    Background
    

    The definition of disease progression (PD) to EGFR TKIs has evolved from RECIST to a combination of clinical and RECIST evaluation. Patients with dramatic, local or gradual progression to third generation EGFR TKIs have been tailored to different subsequent treatment strategies. However, little is known about progression to third generation EGFR TKIs from molecular perspective.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Longitudinal plasma samples were collected from T790M-positive patients who progressed on a third generation EGFR TKI AC0010 in a phase I/II study in Guangdong Lung Cancer Institute. A pre-defined and unified molecular and radiological evaluation of PD were performed. Ultra-deep sequencing capturing 295 cancer-related genes was performed to track the changes in ctDNA to depict molecular PD, which was defined by acquired SNV/SCNV, or ≥20% increase in allelic fraction/copy number of pre-existing SNV /SCNV or both. Radiological PD was defined by RECIST.

    4c3880bb027f159e801041b1021e88e8 Result
    

    As of October 2016, 102 serial plasma samples from 23 patients with clinical PD were included. Three subtypes of PD to AC0010 were revealed (Fig1). Molecular PD occurred prior to radiological PD in 43.5% of patients (10/23), with an average lead time of 3.0 months. Molecular PD occurred concurrently with radiological PD in 39.1% of patients (9/23). Interestingly, 17.4% of patients (4/23) experienced radiological PD prior to molecular PD, with molecular PD occurred during AC0010 continuation beyond progression (CBPD) in 3 patients. Of patients experienced clinical stable PD in extracranial lesions, radiological PD occurring prior to molecular PD group (n=2) demonstrated longer duration of AC0010 CBPD than molecular PD occurring prior to (n=3) or concurrently with radiological PD groups (n=4) (Median, 5.6 months vs. 1.9 months vs. 1.8 months).

    

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our study revealed 3 distinct subtypes of PD to AC0010, providing insights into PD by combining molecular and radiological evaluation and might guide the optimal time for treatment switch and personalized subsequent treatments.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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