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BIOMARKER:

EGFR L861Q + EGFR G719X

i
Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor
Entrez ID:
over3years
Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: Are They Different from Those with Common EGFR Mutations? (PubMed, Biology (Basel))
During the study, 2121 patients with EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common EGFR mutations. T790M was detected in 28.6% of the uncommon EGFR mutation-positive patients for whom prior 1G/2G EGFR-TKIs failed and underwent repeat biopsy at the time of progression.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR L861Q + EGFR G719X • EGFR mutation + EGFR T790M
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erlotinib • Gilotrif (afatinib) • gefitinib
over3years
Allele-specific role of ERBB2 in the oncogenic function of EGFR L861Q in EGFR-mutant lung cancers. (PubMed, J Thorac Oncol)
Our results suggest that ERBB2 plays a previously unrecognized role in EGFR L861Q-driven tumorigenesis, and pan-ERBB inhibitors are likely to be more effective than selective EGFR tyrosine kinase inhibitors in this setting.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MCL1 (Myeloid cell leukemia 1)
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EGFR mutation • EGFR L858R • HER-2 expression • EGFR expression • EGFR L861Q • EGFR G719X • EGFR exon 18 mutation • MCL1 expression • EGFR L861Q + EGFR G719X
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Tagrisso (osimertinib)
over3years
[VIRTUAL] Afatinib in Asian and Non-Asian Patients (pts) with EGFR Mutation-Positive (EGFRm+) NSCLC Harboring Major Uncommon Mutations (IASLC-NACLC 2020)
Afatinib is effective in pts with NSCLC with major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations and some Ins20 mutations, unaffected by ethnicity. Asian pts appeared to have a high proportion of major uncommon mutations, known to be highly sensitive to afatinib.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR mutation + EGFR T790M
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Gilotrif (afatinib)
over3years
Clinical Benefit of Tyrosine Kinase Inhibitors in Advanced Lung Cancer with EGFR-G719A and Other Uncommon EGFR Mutations. (PubMed, Oncologist)
Afatinib treatment at 40 mg daily is associated with high rates of adverse events and dose reductions; alternative strategies including pulse intermittent dosing should be evaluated prospectively. Osimertinib (with favorable safety profile and intracranial penetration) has shown promising results in this population in a phase II trial from South Korea; additional trials are ongoing.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR S768I • EGFR G719A • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR L858R + EGFR exon 19 deletion • EGFR T790M + KRAS mutation • EGFR mutation + EGFR T790M • EGFR G719A + EGFR S768I • EGFR L858R + EGFR S768I • EGFR exon 19 deletion + EGFR S768I • EGFR T790M + exon 19 deletion
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Tagrisso (osimertinib) • Gilotrif (afatinib)
over3years
Successful Treatment of a Patient with Lung Adenocarcinoma Harboring Compound EGFR Gene Mutations, G719X and S768I, with Afatinib. (PubMed, Tokai J Exp Clin Med)
Treatment with afatinib (40 mg/day) produced a partial response, which was maintained for 17 months with continued treatment. A literature review revealed that lung cancer with G719X/S768I compound mutation exhibited good response to EGFR-TKIs, even better than that of lung cancers with single uncommon mutations.
Clinical • Review • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR L858R + EGFR S768I • EGFR exon 19 deletion + EGFR S768I
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Gilotrif (afatinib)
over3years
Osimertinib, an EGFR tyrosine kinase inhibitor, exerts anti-tumor activity in preclinical NSCLC models harboring the uncommon EGFR mutations G719X or L861Q or S768I. (PubMed, Mol Cancer Ther)
We report osimertinib inhibits signalling pathways and cellular growth in G719X mutant cell lines in vitro and demonstrate sustained tumor growth inhibition of PDX harboring the G719X mutation alone or in combination with L861Q and S768I. Together this data supports clinical testing of osimertinib in patients with uncommon EGFR NSCLC.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR mutation + EGFR T790M • EGFR L858R + EGFR S768I
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Tagrisso (osimertinib)
over3years
Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). (PubMed, J Clin Oncol)
Osimertinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.
Clinical • P2 data • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR S768I • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR L858R + EGFR exon 19 deletion • EGFR mutation + EGFR T790M • EGFR L858R + EGFR S768I • EGFR exon 19 deletion + EGFR S768I • EGFR T790M + exon 19 deletion
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Tagrisso (osimertinib)
over3years
TAS6417/CLN-081 is a pan-mutation-selective EGFR tyrosine kinase inhibitor with a broad spectrum of preclinical activity against clinically-relevant EGFR mutations. (PubMed, Mol Cancer Res)
Lung cancer and genetically engineered cell lines, as well as murine xenograft models were used to evaluate the efficacy of TAS6417 and other approved/in-development EGFR TKIs (erlotinib, afatinib, osimertinib, and poziotinib). Taken together, we demonstrate that TAS6417 is a potent EGFR TKI with a broad spectrum of activity and a wider therapeutic window than most approved/in-development generations of EGFR inhibitors. Implications: TAS6417/CLN-081 is a potent EGFR TKI with a wide therapeutic window and may be effective in lung cancer patients with clinically relevant EGFR mutations.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR L858R + EGFR exon 19 deletion • EGFR L858R + EGFR S768I • EGFR exon 19 deletion + EGFR S768I • EGFR T790M + exon 19 deletion
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Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • Pozenveo (poziotinib) • zipalertinib (CLN-081)
over3years
Evaluation of PCR-HRM, RFLP, and direct sequencing as simple and cost-effective methods to detect common EGFR mutations in plasma cell-free DNA of non-small cell lung cancer patients. (PubMed, Cancer Rep (Hoboken))
Despite low sensitivity, combined DS, RFLP, and PCR-HRM was able to detect EGFR mutations in plasma cfDNA with high specificity. Moreover, TKI resistance exon 20 insertions mutation was detected as early as 3 months post TKI treatment.
Clinical • Journal • HEOR
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR G719A • EGFR G719S • EGFR exon 18 mutation • EGFR G719C • EGFR L861Q + EGFR G719X • EGFR G719S + EGFR L861Q
over3years
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR mutation + EGFR T790M
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Gilotrif (afatinib)
almost4years
Clinical Activity of Afatinib in Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Spanish Retrospective Multicenter Study. (PubMed, Clin Lung Cancer)
In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.
Retrospective data • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861Q + EGFR G719X
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Gilotrif (afatinib)
almost4years
[VIRTUAL] Different subtypes of EGFR mutations exhibit distinct patterns of TMB and PD-L1 in patients with non-small cell lung cancer (AACR-II 2020)
This study’s findings reveal that different EGFR mutation subtypes display heterogeneous immunotherapeutic features, and EGFR G719X was associated with an increased TMB, a higher proportion of TMB-H/PD-L1 positive patients, and fewer concurrent copy number amplification GAs. This suggests that GAs of G719X may have implications as a biomarker for guiding ICI treatment in EGFR-mutated NSCLC.
Clinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • LRP1B (LDL Receptor Related Protein 1B)
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PD-L1 expression • EGFR mutation • TMB-H • EGFR L858R • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR L861Q + EGFR G719X • EGFR T790M + exon 19 deletion
almost4years
Clinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L861Q • EGFR G719X • EGFR L861Q + EGFR G719X
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Gilotrif (afatinib)
almost4years
Comparison of the characteristics of uncommon epidermal growth factor receptor (EGFR) mutations and EGFR-tyrosine kinase inhibitor treatment in patients with non-small cell lung cancer from different ethnic groups. (PubMed, Exp Ther Med)
There were marked differences between individuals regarding the efficacy of EGFR-TKI treatment and the survival time of patients with uncommon EGFR mutations, second-line EGFR-TKIs had a lower ORR and DCR while had a longer mPFS. All of these could provide a basis for the exploration of different regimens for patients with different types of uncommon mutations.
Clinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR expression • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L861Q + EGFR G719X
almost4years
[VIRTUAL] Evaluation of the fully automated Idylla EGFR Mutation Assay in Chinese patients with lung adenocarcinoma. (ASCO 2020)
"The Idylla system provides a rapid, accurate and user-friendly solution to EGFR characterization, especially in time-sensitive scenarios where special expertise and staff training could be a challenge. Research Funding: None"
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR L858R + EGFR S768I
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Idylla™ EGFR Mutation Test
almost4years
[VIRTUAL] Clinical and molecular characteristics of the patients in the liquid biopsy study in mEGFR-NSCLC in a Spanish population (OPH-1). (ASCO 2020)
The first-line treatment was afatinib in 47.5%, erlotinib in 21.5% and gefitinib in 31%. We concluded that the clinical characteristics of the patients of the OPH study are consistent with the previous reported in the Caucasian population and the subgroups with the worst prognosis include the squamous histology, the G719X mutation and the liver metastasis. Research Funding: BOEHRINGER INGELHEIM
Clinical • Liquid biopsy
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR L861Q + EGFR G719X
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erlotinib • Gilotrif (afatinib) • gefitinib
almost4years
[VIRTUAL] Osimertinib in non-small cell lung cancer (NSCLC) with atypical EGFR activating mutations: A retrospective multicenter study. (ASCO 2020)
In this largest known clinically annotated dataset of patients with atypical EGFR-mutations treated with osi, activity was noted, though 1L clinical benefit on osi appears lower in this multicenter US cohort than in E19del or L858R. These results are comparable to the recently published prospective phase II trial (Cho et al, 2019) conducted in Korea. Patients with L861Q and Exon 19 insertion appeared to benefit the most from osi in this time on treatment retrospective analysis.
Retrospective data
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + EGFR T790M • EGFR G719X • EGFR S768I • EGFR G719X + EGFR S768I • EGFR L861Q + EGFR G719X • EGFR T790M + exon 19 deletion
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Tagrisso (osimertinib)