Abstract 1974
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Ten mL of venous blood was withdrawn and plasma samples were stored at -20 °C until delivered to central laboratory.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. < 40 mg final dose groups.
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.
Editorial acknowledgement
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.
Resources from the same session
681 - Significance of the red blood cell distribution width in resected pathological stage I non-small cell lung cancer
Presenter: Gouji Toyokawa
Session: Poster Display session 1
Resources:
Abstract
3336 - Survival outcome of non-small cell lung cancer (NSCLC) patients: Comparing results between the database of the Comprehensive Cancer Center Zürich (CCCZ) and the Epidemiological Cancer Registry Zurich and Zug (KKR)
Presenter: Rolf A. Stahel
Session: Poster Display session 1
Resources:
Abstract
2204 - NORA trial (GECP 15/02): Updated results of the Spanish Lung Cancer Group (SLCG) phase II trial of concurrent chemo-radiotherapy (CT-RT) with cisplatin (P) plus metronomic oral vinorelbine (mOV) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC)
Presenter: María Guirado
Session: Poster Display session 1
Resources:
Abstract
1446 - A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators set by principle component analysis
Presenter: Bo Cheng
Session: Poster Display session 1
Resources:
Abstract
1788 - Prognostic and predictive value of 18F-PET/CT on the response to treatment in locally advanced non-small cell lung cancer (NSCLC)
Presenter: Cristina Alfaro Autor
Session: Poster Display session 1
Resources:
Abstract
2299 - Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non small cell lung cancer
Presenter: Abdurrahman Işıkdoğan
Session: Poster Display session 1
Resources:
Abstract
4211 - Predicting the first failure pattern in patients with inoperable local advanced non-small cell lung cancer (LA-NSCLC) receiving definitive chemoradiotherapy: Establishment and internal validation of a nomogram based on the clinicopathological factors
Presenter: Xueru Zhu
Session: Poster Display session 1
Resources:
Abstract
1550 - Prognostic impact of neutrophil-to-lymphocyte ratio (NLR) pre and post chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC)
Presenter: Vicente Palomar Abril
Session: Poster Display session 1
Resources:
Abstract
2345 - Meta-analysis evaluating neutropenia incidence with EGFR inhibitors and chemotherapy in patients with NSCLC
Presenter: Bernardo Rapoport
Session: Poster Display session 1
Resources:
Abstract
3747 - Effector CD4+ T-cell induction by thoracic radiotherapy for patients with NSCLC
Presenter: Yu Miura
Session: Poster Display session 1
Resources:
Abstract