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Ten mL of venous blood was withdrawn and plasma samples were stored at -20 °C until delivered to central laboratory.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
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract
5052 - Identification of first-in-class, naturally occurring LAG3 checkpoint inhibitor
Presenter: Gennady Bratslavsky
Session: Poster Display session 1
Resources:
Abstract
5336 - Are Epigenetic therapies modifying sensitivity to conventional chemotherapy?
Presenter: Alexandra Bizot
Session: Poster Display session 1
Resources:
Abstract
5739 - Oncogenic mutations at the dimer interface of EGFR lead to formation of covalent homo-dimers and allosteric activation of the kinase domain: A mechanism which alters the selectivity profile of oncogenic EGFR.
Presenter: Elizabeth Buck
Session: Poster Display session 1
Resources:
Abstract
5492 - Basic selective estrogen receptor degraders (B-SERDs) in combination with novel BET inhibitors in ER+ breast cancer
Presenter: Rui Xiong
Session: Poster Display session 1
Resources:
Abstract
5965 - EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer
Presenter: Ronan Le Moigne
Session: Poster Display session 1
Resources:
Abstract
3582 - AVID200 neutralizes TGF-beta1 and -beta3, the principal immunosuppressive TGF-beta isoforms overexpressed by tumors, and sensitizes tumors to immune checkpoint inhibitors.
Presenter: Tina Gruosso
Session: Poster Display session 1
Resources:
Abstract
1996 - High NAMPT expression and anti-tumor activity of NAMPT inhibitor in adult T-cell leukemia/lymphoma
Presenter: Tomohiro Kozako
Session: Poster Display session 1
Resources:
Abstract
4307 - TPX-0046 is a novel and potent RET/SRC inhibitor for RET-driven cancers
Presenter: Alexander Drilon
Session: Poster Display session 1
Resources:
Abstract
4869 - In Vivo Evaluation of Cisplatin-loaded PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery
Presenter: Yingtzu Yen
Session: Poster Display session 1
Resources:
Abstract