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BIOMARKER:

EGFR G724S

i
Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor
Entrez ID:
3ms
Trial completion date • Trial primary completion date • Metastases
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR G724S • HER-2 exon 23 mutation • EGFR R776C • EGFR V774M
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Ivesa (furmonertinib)
4ms
Phase classification • Metastases
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR G724S • HER-2 exon 23 mutation • EGFR R776C • EGFR V774M
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Ivesa (furmonertinib)
8ms
Benefits of Afatinib and Osimertinib in a Patient with Lung Adenocarcinoma Harboring EGFR19Del/T790M/G724S Mutation (IASLC-WCLC 2023)
She was treated with intrathoracic infusion chemotherapy (pemetrexed 200mg+nedaplatin 20mg) on October 11, 2018...Based on the above findings, the patient was administered with gefitinib 250 mg daily as first-line therapy on November 15, 2018, and achieved partial response (PR)...On January 25, 2022, the patient was hospitalized for shortness of breath, and received intrathoracic Infusion chemotherapy (cisplatin 80mg)... The combination therapy of afatinib and osimertinib could be a new therapeutic option for patients with lung adenocarcinoma harboring EGFRG724S/T790M/19Del mutation.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR exon 19 deletion • EGFR T790M • EGFR negative • EGFR G724S • EGFR T790M negative
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cisplatin • Tagrisso (osimertinib) • Gilotrif (afatinib) • gefitinib • pemetrexed • Aqupla (nedaplatin)
over1year
Long-term response in a patient with adenocarcinoma harboring both common and uncommon EGFR mutations. (PubMed, Invest New Drugs)
Recently, we read a paper "Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation" published in Investigational New Drugs. To share our experience, we present a case of 58-year-old man with a long-term response to afatinib in a patient with previously unreported compound EGFR mutation. In patients with rare compound EGFR mutations, afatinib might be one of the treatment option.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR exon 19 deletion • EGFR G724S
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Gilotrif (afatinib) • Vizimpro (dacomitinib)
over1year
Non-small cell lung cancer harboring EGFR G724S mutation and exon 19 deletion responded to afatinib monotherapy after multiple lines of target therapies. (PubMed, Anticancer Drugs)
A patient diagnosed with advanced EGFR-mutated (exon 19 deletion) NSCLC after several lines of treatment - gefitinib, osimertinib, heat shock protein inhibitors and chemotherapy-developed EGFR G724S mutation retaining the exon 19 deletion. She was then treated successfully with afatinib leading to a progression free survival of 9 months (and counting). This is the first report of the emergence of G724S mutation, together with ex19del, after three subsequent lines of therapy following progressive disease to Osimertinib, and we report for the first time the activity of afatinib against EGFR exon 18 G724S mutation in this setting.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR exon 19 deletion • EGFR exon 18 mutation • EGFR G724S
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Tagrisso (osimertinib) • Gilotrif (afatinib) • gefitinib
over1year
Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation; a case report. (PubMed, Invest New Drugs)
Dacomitinib may be effective choice in afatinib-refractory carcinomatous meningitis harboring G724S mutation. This is the first case report showing that a change to dacomitinib responded to afatinib refractory cancerous meningitis.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR exon 19 deletion • EGFR G724S • EGFR E746
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Gilotrif (afatinib) • Vizimpro (dacomitinib)
almost2years
Developing of EGFR resistant mutations to Tyrosine Kinase Inhibitors (TKI) in Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2022)
Acquired resistance in EGFR mutant NSCLC remains very heterogeneous; the frequency of individual mutations is low, one of the reasons might be lack of testing at resistance. While T790M and C797S mutations are well described, this report also documents a significant number of L718V mutations, primarily in osimertinib-treated pts with an original L858R. These data support the need to increase NGS evaluation of patients with EGFR mutant lung cancers who have developed clinical resistance.
PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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PD-L1 expression • TP53 mutation • EGFR mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR T790M + EGFR C797S • EGFR G724S
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PD-L1 IHC 22C3 pharmDx
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Tagrisso (osimertinib)
almost2years
Efficacy of dacomitinib in patients with non-small cell lung cancer carrying complex EGFR mutations: a real-world study. (PubMed, J Thorac Dis)
This study indicated a worse response and prognosis of patients with NSCLC harboring complex EGFR mutations than those harboring common EGFR mutations when treated with dacomitinib. Further studies and data are needed to confirm this conclusion.
Journal • Real-world evidence
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR exon 18 mutation • EGFR G724S • EGFR K754E
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Vizimpro (dacomitinib)
almost2years
Afatinib for the Treatment of Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: An Updated Database of 1023 Cases Brief Report. (PubMed, Front Oncol)
Afatinib should be considered as a first-line treatment option for NSCLC patients with major uncommon, compound, 'other' (including E709X and L747X) and some specific exon 20 insertion mutations. Moderate activity was seen against osimertinib resistance EGFR mutations.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR L861Q • EGFR C797S • EGFR G719X • EGFR S768I • EGFR G724S
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Tagrisso (osimertinib) • Gilotrif (afatinib)
almost2years
Identification of pretreatment genomic biomarkers and mechanisms of acquired resistance to first-line osimertinib in advanced EGFR-mutant lung cancers. (ASCO 2022)
Pts with an identified mechanism of resistance did not have improved post-progression survival (12 mo HR 1.6, p = 0.09), but receiving next line of therapy based on post-progression tumor biopsy results (including platinum-etoposide for transformation) did improve post-progression survival (12 mo HR 0.4, p = 0.01). Pts with atypical EGFR drivers or concurrent TP53+/-RB1 alterations have significantly shorter rwPFS on first line osimertinib, highlighting need for additional interventions for these patients. Given the high frequency of transformation and improvement in post-progression survival by tailoring next line of therapy to the identified mechanism, pts with EGFR-mutant lung cancer on first line osimertinib may benefit from tissue biopsies at progression. For pts without an identified resistance mechanism by NGS, additional methods of interrogating tumors at progression are needed.
Preclinical • Clinical
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4)
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KRAS mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR amplification • EGFR C797S • KRAS G12A • KRAS G12 • EGFR mutation + PIK3CA mutation • EGFR G724S
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MSK-IMPACT
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Tagrisso (osimertinib) • etoposide IV
over2years
Afatinib as a Potential Therapeutic Option for Patients With NSCLC With EGFR G724S. (PubMed, JTO Clin Res Rep)
In the subset who had progressed on osimertinib, afatinib also yielded a superior progression-free survival (6.2 mo) than non-afatinib therapies (1.0 mo, HR = 0.04, p = 0.005) and alternative EGFR TKIs (1.8 mo, HR = 0.06, p = 0.033). EGFR G724S emerges as a resistant mutation against EGFR TKI preferentially in the context of a rare variant of 19del, whereas it might mediate differential mechanisms in the context of exon 20 mutation. We also found that afatinib could be a potential therapeutic option for patients with NSCLC with G724S.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR exon 19 deletion • MET amplification • EGFR T790M • EGFR exon 20 insertion • EGFR exon 21 mutation • EGFR S768I • EGFR exon 20 mutation • EGFR E746_S752delinsV • EGFR G724S • EGFR E746
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Tagrisso (osimertinib) • Gilotrif (afatinib)
over2years
Successful treatment of Afatinib reversing EGFR Ex19Del/G724S resistance guided by protein-drug docking. (PubMed, Oncologist)
We analysed the interaction of three drugs(Afatinib, Gefitinib, Osimertinib) with EGFR from three aspects: the spatial structure of the binding region, the scoring function value and the interaction force between drug molecules and active center of EGFR. Treated with Afatinib, he received a progression-free survival(PFS) of more than 1 year. With the guidance of this case report, we provide the clinical evidence of using Afatinib for G724S-mutant patients and obtain long-term clinical survival.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR exon 19 deletion • EGFR G724S
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Tagrisso (osimertinib) • Gilotrif (afatinib) • gefitinib
over2years
[VIRTUAL] Afatinib for the treatment of NSCLC with uncommon EGFR mutations: An updated database of 1023 cases (ESMO 2021)
15 pts with known acquired EGFR resistance mutations to osimertinib (osi; G724S, L718X, C797S) were given afa post osi: ORR: 36%. Afa showed activity against major uncommon, compound, other (including E709X and L747X) and some specific ex20ins mutations. Afa showed activity against major uncommon, compound, other (including E709X and L747X) and some specific ex20ins mutations. The data support the use of afa in these settings. Moderate activity was seen post-osi.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR C797S • EGFR G719X • EGFR S768I • EGFR G724S
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Tagrisso (osimertinib) • Gilotrif (afatinib)
over2years
Pilot Study of Dacomitinib for Patients With Metastatic EGFR-Mutant Lung Cancers With Disease Progression After Initial Treatment With Osimertinib. (PubMed, JCO Precis Oncol)
In the first trial evaluating a second-generation EGFR TKI after first-line third-generation osimertinib, we found that dacomitinib after disease progression on osimertinib has limited benefit.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • EGFR C797S • MET mutation • EGFR G719A • EGFR G724S
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Tagrisso (osimertinib) • Vizimpro (dacomitinib)
almost3years
Fighting tertiary mutations in EGFR-driven lung-cancers: current advances and future perspectives in medicinal chemistry. (PubMed, Biochem Pharmacol)
Third-generation inhibitors of the epidermal growth factor receptor (EGFR), best exemplified by osimertinib, have been developed to selectively target variants of EGFR bearing activating mutations and the mutation of gatekeeper T790 in patients with EGFR-mutated forms of Non-Small Cell Lung Cancer (NSCLC)...The challenge of overcoming newly developed and recurrent resistances mediated by EGFR-mutations is thus driving the search of alternative strategies in the design of new therapeutic agents able to block EGFR-driven tumor growth. In this manuscript we review the recently emerged EGFR-dependent mechanisms of resistance to third-generation inhibitors, and the achievements lately obtained in the development of next-generation EGFR inhibitors.
Review • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR C797S • TERT mutation • EGFR G724S • EGFR L718Q
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Tagrisso (osimertinib)
almost3years
[VIRTUAL] Incidence and heterogeneity of C797S and other EGFR resistance mutations on routine comprehensive genomic profiling (CGP). (ASCO 2021)
Funding: Foundation Medicine Background: The emergence of osimertinib (osi) as standard of care therapy for EGFR-mutant NSCLC has led to investigations into understanding and overcoming drug resistance... Osi resistance in EGFR-mutant NSCLC is a poor prognosis condition . EGFR C797S is a recurring resistance mut which, in a minority of cases, can co-occur with alternate on and off target resistance muts detected with tissue and liquid biopsy.
IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CCDC6 (Coiled-Coil Domain Containing 6) • STRN (Striatin)
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BRAF V600E • EGFR mutation • HER-2 amplification • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • RET fusion • FGFR3-TACC3 fusion • ALK fusion • EGFR C797S • CCDC6-RET fusion • EGFR S768I • BRAF fusion • EGFR G719A • FGFR3 fusion • STRN-ALK fusion • EGFR G724S • EGFR L718Q • EGFR G796S
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Tagrisso (osimertinib)
3years
Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib in EGFR-Mutant Lung Cancer. (PubMed, Clin Cancer Res)
Histologic transformation and other off-target molecular alterations are frequent early emerging resistance mechanisms to osimertinib and are associated with poor clinical outcomes.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGF (Fibroblast Growth Factor)
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KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • MET amplification • RET fusion • RET mutation • MET mutation • BRAF fusion • EGFR mutation + PIK3CA mutation • EGFR G724S • BRAF amplification • FGF amplification
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Tagrisso (osimertinib)
over3years
[VIRTUAL] Afatinib as a Potential Therapeutic Option for Non-small Cell Lung Cancer Patients with EGFR G724S (IASLC-WCLC 2020)
Results EGFR G724S was identified from 2 patients prior to the administration of any treatment, (baseline) from 1 patient after gefitinib failure and from 5 patients after osimertinib failure. Conclusion Our study provides clinical evidence that afatinib monotherapy could be a potential therapeutic option for NSCLC patients with EGFR G724S. Further studies for evaluating the efficacy of afatinib in advanced NSCLC patients harboring EGFR G724S and the underlying resistance mechanism are warranted.
Clinical
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene)
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BRAF V600E • EGFR mutation • BRAF V600 • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR C797S • EGFR S768I • EGFR exon 20 mutation • EGFR exon 18 mutation • EGFR E746_S752delinsV • EGFR G724S • EGFR E746
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Tagrisso (osimertinib) • Gilotrif (afatinib) • gefitinib
over3years
[VIRTUAL] A Novel EGFR G724S and R776H Rare Co-Mutation Response to Afatinib in a Patient With Lung Adenocarcinoma (IASLC-WCLC 2020)
Based on these findings, the patient was administered with afatinib (a dose of 30 mg/d) combined with bevacizumab. Conclusion This is the first report of co-mutation of EGFR R776H/G724S in a patient with lung adenocarcinoma. Afatinib may be a beneficial therapeutic option for a subset of NSCLC with rare EGFR co-mutation.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR positive • EGFR G724S • EGFR R776H
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Avastin (bevacizumab) • Gilotrif (afatinib)
over3years
Acquired resistance to osimertinib in patients with non-small-cell lung cancer: mechanisms and clinical outcomes. (PubMed, J Cancer Res Clin Oncol)
The study revealed heterogeneous mechanisms of resistance to osimertinib in advanced NSCLC patients and their association with clinical outcomes. Patients who maintained T790M mutation or with EGFR-dependent resistance mechanism had longer clinical outcome benefits.
Clinical • Clinical data • Retrospective data • Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
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TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • MET amplification • EGFR T790M • EGFR amplification • EGFR C797S • PIK3CA amplification • EGFR mutation + KRAS mutation • EGFR G724S • BRAF mutation + MET amplification • EGFR T790M + KRAS mutation • EGFR mutation + EGFR T790M • EGFR C796S • EGFR C797S + EGFR C796S • EGFR E758D • EGFR G796S • EGFR V802I • EGFR V834L • EGFR mutation + EGFR T790M + EGFR C797S • KRAS mutation + EGFR amplification
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Tagrisso (osimertinib)
almost4years
The clinical efficacy of combinatorial therapy of EGFR-TKI and crizotinib in overcoming MET amplification-mediated resistance from prior EGFR-TKI therapy. (PubMed, Lung Cancer)
Our study provides clinical evidence of the efficacy of combinatorial regimen with either first- or third-generation EGFR-TKI and crizotinib after the emergence of MET amplification-mediated EGFR-TKI resistance in patients with EGFR-mutant NSCLC.
Clinical • Journal
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CCDC6 (Coiled-Coil Domain Containing 6)
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EGFR mutation • MET amplification • RET fusion • EGFR C797S • EGFR G724S • EGFR L718Q
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Xalkori (crizotinib) • Tagrisso (osimertinib) • erlotinib • gefitinib • Conmana (icotinib)