Abstract 564P
Background
The current National Comprehensive Cancer Network guideline recommends Afatinib and/or Osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC carrying EGFR p.G719X mutation. In the absence of head-to-head trials comparing Afatinib with Osimertinib in EGFR p.G719X mutant patients, it is unclear which regimen is the preferred treatment option.
Methods
A large cohort of 4228 treatment-naïve patients with lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened in terms of the EGFR p.G719X mutation. Ba/F3 cells stably expressing the EGFR p.G719A mutation with either the p.E709K mutation or not were created to investigate the response to EGFR-TKIs. The patient-derived lung cancer organoid (LCO) cultures were created, and the corresponding drug treatments and sensitivity (DTS) test was performed.
Results
EGFR p.G719X mutation occurs with a prevalence of 2.56%. EGFR p.E709X(30.4%) composed the most frequent co-occurring EGFR mutation. Co-occurring EGFR p.E709X mutations exerted a detrimental effect on outcomes in Osimertinib-treated patients (G719X/E709X VS. G719X; ORR: 0.00% VS. 47.62%, P<0.001; mPFS:7.18 VS. 14.2 months, P=0.042; respectively). In contrast, no significant difference was found in the treatment efficacy between EGFR p.G719X/E709X and EGFR p.G719X patients upon Afatinib treatment (G719X/E709X VS. G719X; ORR: 71.43% VS. 56.67%, P=0.99; mPFS:14.7 VS. 15.8 months, P=0.69; respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation treated with the third-generation EGFR-TKIs. The DTS result of LCO revealed that the second-generation EGFR-TKIs may be superior to first or third-generation EGFR-TKIs for patients with EGFR p.G719X/E709X mutation.
Conclusions
We enrolled the largest available dataset of EGFR p.G719X-mutant patients with NSCLC. The variable sensitivity of EGFR p.G719X mutation to different EGFR TKIs indicates that a personalized treatment strategy should be undertaken in patients depending on the status of underlying co-existing EGFR p.E709X mutation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
87TiP - Phase I expansion study of the tissue factor (TF)–targeting antibody-drug conjugate (ADC) XB002 as a single-agent and combination therapy in patients with advanced solid tumors (JEWEL-101)
Presenter: Mustafa Syed
Session: Poster Display
Resources:
Abstract
88TiP - A phase Ib study of HMBD-001, a monoclonal antibody targeting HER3, with or without chemotherapy in patients with genetic aberrations in HER3 signaling
Presenter: Nick Pavlakis
Session: Poster Display
Resources:
Abstract
93P - Efficacy and safety of fruquintinib (F) + best supportive care (BSC) vs placebo (P) + BSC in refractory metastatic colorectal cancer (mCRC): Asian vs non-Asian outcomes in FRESCO-2
Presenter: Daisuke Kotani
Session: Poster Display
Resources:
Abstract
94P - Sidedness-dependent prognostic impact of gene alterations in metastatic colorectal cancer in the nationwide cancer genome screening project in Japan (SCRUM-Japan GI-SCREEN)
Presenter: Takeshi Kajiwara
Session: Poster Display
Resources:
Abstract
95P - Interim results of a prospective randomized controlled study to compare the clinical outcomes of total neoadjuvant therapy vs long course chemoradiotherapy in locally advanced carcinoma rectum
Presenter: Sandip Barik
Session: Poster Display
Resources:
Abstract
96P - Tyrosine kinase inhibitor (TKI) plus PD-1 blockade in TKI-responsive MSS/pMMR metastatic colorectal adenocarcinoma (mCRC): Updated results of TRAP study
Presenter: Jingdong Zhang
Session: Poster Display
Resources:
Abstract
97P - Asian subgroup analysis of the phase III LEAP-017 trial of lenvatinib plus pembrolizumab vs standard-of-care in previously treated metastatic colorectal cancer (mCRC)
Presenter: Rui-Hua Xu
Session: Poster Display
Resources:
Abstract
98P - Real clinical impact of postoperative surgical complications after colon cancer surgery
Presenter: Toru Aoyama
Session: Poster Display
Resources:
Abstract
99P - Extended lymphadenectomy may not be necessary for MSI-H colon cancer patients after immunotherapy
Presenter: Rongxin Zhang
Session: Poster Display
Resources:
Abstract
100P - Identification of phenomic data in the pathogenesis of colorectal cancer: A UK biobank data analysis
Presenter: Shirin Hui Tan
Session: Poster Display
Resources:
Abstract