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
602P - COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib (Enco) + binimetinib (Bini) vs vemurafenib (Vemu) or Enco in patients (Pts) with BRAF V600-mutant melanoma
Presenter: Andrew Haydon
Session: Poster Display
Resources:
Abstract
603P - An individualised postoperative radiological surveillance schedule for IDH-wildtype glioblastoma patients (HK-GBM Registry)
Presenter: Jason Chak Yan Li
Session: Poster Display
Resources:
Abstract
604P - Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who progressed after prior VEGFR-targeted therapy: Outcomes from COSMIC-311 by BRAF status
Presenter: Marcia Brose
Session: Poster Display
Resources:
Abstract
606P - BRAF and NRAS mutations are associated with poor prognosis in Asians with acral-lentiginous and nodular cutaneous melanoma
Presenter: Sumadi Lukman Anwar
Session: Poster Display
Resources:
Abstract
607P - Single institutional outcomes of radiotherapy and systemic therapy for melanoma brain metastases in Japan
Presenter: Naoya Yamazaki
Session: Poster Display
Resources:
Abstract
608P - The efficacy of immune checkpoint inhibitors and targeted therapy in mucosal melanomas: A systematic review and meta-analysis
Presenter: Andrea Teo
Session: Poster Display
Resources:
Abstract
609P - The association between thyroid function abnormalities and vitiligo induced by pembrolizumab regarding prognosis in patients with advanced melanoma
Presenter: Moez Mobarek
Session: Poster Display
Resources:
Abstract
610P - Analyzing the clinical benefit of the evidence presented at these congresses and utilizing a standardized scale to quantify it will significantly enhance our understanding of the studies showcased, allowing for more objective evaluation and interpretation
Presenter: Charles Jeffrey Tan
Session: Poster Display
Resources:
Abstract
611P - ESMO-magnitude of clinical benefit scale (MCBS) scores for phase III trials of adjuvant and curative therapies at the 2022 ASCO annual meeting (ASCO22)
Presenter: Thi Thao Vi Luong
Session: Poster Display
Resources:
Abstract
612P - Is the juice worth the squeeze? Overall survival gain per unit treatment time as a metric of clinical benefit of systemic treatment in incurable cancers
Presenter: Vodathi Bamunuarachchi
Session: Poster Display
Resources:
Abstract