1539PA phase II open-label, multicentre study to assess the anti-tumour activity of afatinib in patients with activating epidermal growth factor receptor mutation (EGFRm) from circulating tumour DNA (CtDNA)

Abstract Background The treatment efficacy of afatinib was assessed in patients with lung cancer harboring EGFRm which were detected from CtDNA. Primary objective was to prove overall response rate (ORR), and the secondary endpoints were progression free survival (PFS), overall survival and safety. Methods Ten mL of venous blood was withdrawn and plasma samples were stored at -20 °C until delivered to central laboratory. EGFRm analyses for CtDNA were performed by PANA Mutyper® EGFR kit (Panagene, Korea). EGFRm testing for tumor DNA were performed by in-house testing in each hospital with PNA clamp EGFR mutation kit or PANA Mutyper® EGFR kit. Results A total of 331 patients were screened for this trial from 2015 to 2018 March. Tumor genotyping showed 24.5% (81/331), while CtDNA showed 20.5% (68/331) of positivity to detect activating EGFRm (exon 19 deletions or exon 21 point mutations). Among 81 subjects with tumor DNA EGFRm positive subjects, 48 showed EGFRm in their CtDNA (59% sensitivity). Types of EGFRm were completely matched between tumor DNA and CtDNA in 48 subjects. Afatinib (40mg) was initiated in 21 (female:17, adenocarcinoma:20, NSCLC-NOS:1) subjects with mean age of 68.5 years (standard deviation 8.7). Dose modifications were made in 14 subjects (66.7%). Partial remission was observed in 13, stable disease in 5, progression in 1 and response was not evaluated in 2 subjects (ORR : 68.4% in response evaluable subjects). Eleven subjects showed EGFRm only in CtDNA (tumor DNA EGFR wild or unknown, Group 1), and 10 subjects revealed same EGFRm in their CtDNA and tumor DNA (Group 2).There was no significant difference (p = 0.35) in ORR between Group 1 (80.0%) and Group 2 (55.6%). As of April 2019, treatment is ongoing in 7 subjects, 1 withdrew consent, 2 discontinued treatment due to serious adverse events (SAEs). Seven SAEs including 2 drug induced lung disease were reported. Median PFS was 366 days, and there is no difference in PFS between Group1 vs. Group 2, and 40 mg vs. Conclusions Afatinib showed similar ORR and PFS in subjects with NSCLC harboring EGFRm in their CtDNA regardless of tumor EGFRm results. Clinical trial identification NCT02629523, December 14, 2015. Legal entity responsible for the study The authors. Funding Boehringer Ingelheim and Panagene. Disclosure Y. Kim: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche. I. Oh: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche. All other authors have declared no conflicts of interest.