1527P - Sequential treatment with afatinib followed by 3rd generation EGFR-TKI – subgroup analysis of the GIDEON trial: A prospective non-interventional study (NIS) in EGFR mutated NSCLC patients in Germany

Abstract

BackgroundAfatinib and osimertinib both inhibit sensitizing EGFR mutations (deletion 19 and L858R). In addition, osimertinib is highly active against the most frequent resistance mutation (∼60%) T790M and was originally registered for these patients (pts.). Some evidence suggests that a sequential treatment approach using 1st or 2nd gen EGFR-TKIs like afatinib in first-line, followed by a 3rd gen EGFR-TKI in T790M positive pts. may lead to overall survival rates up to 80% after 4 years. Here, we report first results of prospectively collected data within the German NIS GIDEON on pts. treated with 1st line afatinib followed by osimertinib. Methods151 EGFR-mutated NSCLC pts. were treated with afatinib according to label until progression, death or treatment discontinuation. Data on effectiveness (ORR, DCR, PFS and 24 months OS rate) were prospectively assessed for pts. who have been treated with osimertinib following afatinib. ResultsA total of 30/151 (20%) pts. were treated with 1st line afatinib followed by osimertinib. 22 (73%), 7 (23%) and 1 (3%) of these pts. were initially positive for Del19, L858R and G719C, respectively. The mPFS from start of afatinib to PD under osimertinib at the time of analysis was 32.2mo, 29.8mo and NR (95% CI 16.4mo - NR) for the total population, pts. with Del19 and pts. with L858R, respectively. The 24-mo-OS rate was 89.3% for all 30 pts receiving osimertinib in a later line, and 90% and 85.7% for patients with initial Del19 and L858R, respectively. ConclusionsThese data support the evidence that pts. with acquired T790M under afatinib may benefit from sequential TKI treatment. The frequency of T790M was higher in pts. initially tested positive for Del19, which is in line with recently published data. This analysis is limited by the small patient number, explainable by the restricted availability of osimertinib during the study conduct (March 2014 – Dec 2017). Clinical trial identificationNCT02047903. Legal entity responsible for the studyBoehringer Ingelheim. FundingBoehringer Ingelheim. DisclosureW. Brückl: Advisory / Consultancy: AbbVie; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Chugai; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Stratifyer. M. Reck: Honoraria (self), Advisory / Consultancy: Abbot; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Merck. J. Rawluk: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS. R.M. Huber: Speaker Bureau / Expert testimony: ARIAD; Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Clovis Oncology; Research grant / Funding (institution): Pierre Fabre; Speaker Bureau / Expert testimony: Pfizer. C. Hoffmann: Full / Part-time employment: Boehringer Ingelheim. A. Schueler: Full / Part-time employment: Boehringer Ingelheim. All other authors have declared no conflicts of interest.