Abstract 1356P
Background
15–40% of NSCLC adenocarcinoma patients harbor EGFR sensitizing mutations. Tyrosine kinase inhibitors (TKI) provide significant clinical benefit in this population, yet all patients will develop resistance. Liquid biopsy has been demonstrated to reliably identify tumor associated somatic EGFR mutations. Quantitative assessment of mutated EGFR driven tumors could potentially be used to monitor disease progression, to assess therapeutic response, and to identify resistance mechanisms.
Methods
106 longitudinal plasma samples from 16 NSCLC patients treated with osimertinib in first/ second line therapy were analyzed. Samples during treatment and at the time of disease progression were analyzed with the AVENIO ctDNA Surveillance kit*. Mutations at each time point were identified and reported by the AVENIO software v2.0*. The mutation profile of each patient at different timepoints was examined with the treatment and outcome data.
Results
EGFR sensitizing mutations were detected in all plasma samples by sequencing except in 3 cases. Patients responsive to anti-EGFR therapy had a rapid decrease of EGFR driver mutations to non-detectable levels. Patients who had stable or rapid disease progression had stable or decreasing ctDNA levels after receiving treatment. One patient had MET amplification, FBXL7 SNV, and EGFR T790M detected at the time of disease progression, which were not detected at baseline. One patient had EGFR L858R and T790M mutations and progressed very quickly on erlotinib. While detection of T790M mutation decreased upon osimertinib administration, L858R level stayed the same. TP53 mutations were elevated in 3 patients at the time of progression and could potentially be related to anti-EGFR resistance.
Conclusions
This study clearly demonstrated that liquid biopsy could identify resistance mutations beyond EGFR prior to clinical progression. Plasma samples collected prior to or at disease progression could facilitate identification of novel resistant mutations to TKI therapy. Further studies to demonstrate the clinical utility of serial blood EGFR testing in NSCLC management are necessary. *For Research Use Only. Not for use in diagnostic procedures.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Roche Sequencing Solutions, Inc.
Funding
Roche Sequencing Solutions, Inc.
Disclosure
C. Ju, S. Yaung, B. Wehnl: Full/Part-time employment: Roche. J. Jiang: Full/Part-time employment: Roche; Shareholder/Stockholder/Stock options: Roche. C. Woestmann: Full/Part-time employment: Roche (Signature Diagnostics). B. Hinzmann: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. M. Thomas: Speaker Bureau/Expert testimony: Lilly, Roche, Celgene, BMS, AbbVie, AstraZeneca and MSD; Advisory/Consultancy: Lilly, Roche, BMS, AbbVie, Celgene, Novartis, Pfizer, AstraZeneca, and MSD. C.P. Heussel: Advisory/Consultancy: Schering-Plough; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Basilea; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Astellas; Advisory/Consultancy: Gilead; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Advisory/Consultancy: Intermune; Advisory/Consultancy: Fresenius; Advisory/Consultancy: Essex; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bracco; Advisory/Consultancy: MEDA; Advisory/Consultancy: Chiesi; Advisory/Consultancy: Siemens; Advisory/Consultancy: Covidien; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Grifolis; Advisory/Consultancy: Bayer. M. Meister: Research grant/Funding (institution): Roche Diagnostics. M. Schneider: Research grant/Funding (institution): Roche. F. Herth: Advisory/Consultancy: Pulmonx, BTG, Uptake Medical, Olympus Medical, and Holaira; Research grant/Funding (institution): Roche Diagnostics. T. Muley: Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche Diagnostics. J.F. Palma: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. All other authors have declared no conflicts of interest.