^
    16d
    Afatinib Combined with Bevacizumab in the Treatment of Patients with Non-Small Cell Lung Cancer Harboring EGFR G719X, S768I or L861Q/P Mutations. (PubMed, Int J Gen Med)
    The side effects were mild to moderate hand-foot-syndrome, hypertension, and proteinuria. Afatinib in combination with bevacizumab are effective and safe in the management of patients with NSCLC harboring EGFR G719X, S768I, L861Q/P single or compound mutations.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Avastin (bevacizumab) • Gilotrif (afatinib)
    20d
    EXCLAIM-2: TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations (clinicaltrials.gov)
    P3, N=354, Active, not recruiting, Takeda | Trial completion date: Dec 2024 --> Jul 2025
    Trial completion date • EGFR exon 20
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    cisplatin • carboplatin • pemetrexed • Exkivity (mobocertinib)
    26d
    Safety and Efficacy of Osimertinib in Patients With Non-Small-Cell Lung Cancer and Uncommon Tumoral Epidermal Growth Factor Receptor Mutations: A Systematic Review and Single-Arm Meta-Analysis. (PubMed, JCO Precis Oncol)
    Osimertinib demonstrated robust response in NSCLC harboring uncommon EGFR mutations, without unanticipated safety concerns.
    Clinical • Retrospective data • Review • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib)
    1m
    Cytotoxicity and inhibitory potential of CUDC-101 in non-small cell lung cancer cells with rare EGFR L861Q mutation. (PubMed, Curr Res Toxicol)
    In this study, the four cell lines containing the L861Q mutation were constructed by CRISPR and the anti-tumour effects of CUDC-101 on them were investigated in vitro by various chemosensitivity methods, with afatinib serving as a positive control. The results demonstrated that CUDC-101 inhibited the proliferation and clonogenic capacity on the four cells through the ERK or AKT pathways, decreased the mitochondrial membrane potential of the cells, blocked the cell cycle and promoted apoptosis. Our findings suggest that CUDC-101 may be a promising treatment option for NSCLC patients with the EGFR exon 18 substitution mutation L861Q.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L861Q • EGFR exon 18 mutation
    |
    Gilotrif (afatinib) • CUDC-101
    1m
    TARGET: A Study of 5 Years of Adjuvant Osimertinib in Completely Resected Epidermal Growth Factor Receptor Mutation (EGFRm) Non-small Cell Lung Carcinoma (NSCLC) (clinicaltrials.gov)
    P2, N=187, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib)
    1m
    Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    KRAS G12C • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • ALK rearrangement • EGFR L861Q • ROS1 positive • KRAS G12 • EGFR exon 20 mutation • MET positive • EGFR negative
    |
    Opdivo (nivolumab) • gemcitabine • docetaxel • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Cyramza (ramucirumab) • Cometriq (cabozantinib capsule) • ABP 206 (nivolumab biosimilar)
    2ms
    ORBITAL: Study of Osimertinib in Patients with a Lung Cancer with Brain or Leptomeningeal Metastases with EGFR Mutation (clinicaltrials.gov)
    P2, N=57, Active, not recruiting, Intergroupe Francophone de Cancerologie Thoracique | Trial completion date: Feb 2024 --> Dec 2024
    Trial completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X
    |
    Tagrisso (osimertinib)
    2ms
    Study to Assess the Efficacy and Safety of Adjuvant Osimertinib in NSCLC With Uncommon EGFRm (clinicaltrials.gov)
    P2, N=51, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 20 mutation
    |
    Tagrisso (osimertinib)
    3ms
    Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    KRAS G12C • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • ALK rearrangement • EGFR L861Q • ROS1 positive • KRAS G12 • EGFR exon 20 mutation • MET positive • EGFR negative
    |
    Opdivo (nivolumab) • gemcitabine • docetaxel • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Cyramza (ramucirumab) • Cometriq (cabozantinib capsule) • ABP 206 (nivolumab biosimilar)
    3ms
    NCI-2021-04325: Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    EGFR mutation • BRAF mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q • EGFR T790M negative
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab)
    3ms
    Study to Assess the Effect of AZD9291 on the Blood Levels of Simvastatin in Patients With EGFRm+ NSCLC (clinicaltrials.gov)
    P1, N=52, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jun 2024
    Trial completion • Trial completion date
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    Tagrisso (osimertinib) • simvastatin
    3ms
    Landscape of co-occurring OncoKB tier 1/2 alterations in EGFR-mutated lung adenocarcinoma (LUAD) harboring common driver alterations using circulating tumor DNA (ctDNA) next generation sequencing (NGS) in Asia and the Middle East (AME) (ESMO Asia 2024)
    Conclusions Comprehensive ctDNA NGS can identify driver EGFR mts and other informative co-alts for patients with LUAD. Frequency and types of such co-alts are mostly similar in AME and other regions.
    Next-generation sequencing • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • FGFR2 fusion • EGFR L861Q • EGFR C797S • EGFR G719X • EGFR S768I • EGFR fusion
    |
    Guardant360® CDx
    3ms
    Case report of a patient with stage IV lung adenocarcinoma and uncommon/compound EGFR mutations who responded to afatinib. (PubMed, Respir Med Case Rep)
    After 2 months of afatinib treatment, significant tumor shrinkage was observed, and the patient's condition remained stable for 1 year. This case highlights the potential effectiveness of afatinib for treating rare stage IV lung adenocarcinoma with these specific EGFR mutations.
    Journal • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L861Q • EGFR E709G
    |
    Gilotrif (afatinib)
    7ms
    From Rarity to Reality: Osimertinib's Promising Horizon in Treating Uncommon EGFR Mutations in Non-Small Cell Lung Cancer. (PubMed, Clin Cancer Res)
    While afatinib, a second-generation EGFR-TKI, has received FDA approval for patients with these uncommon EGFR mutations, the approval was based on a post-hoc analysis of randomized clinical trials. By synthesizing these findings, we aim to guide oncologists towards more informed decisions in employing TKIs for NSCLC with uncommon EGFR mutations other than exon 20 insertion. Additionally, we explore potential treatment strategies tailored to these patient populations to address the challenges posed by these mutations.
    Clinical • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR exon 18 mutation
    |
    Tagrisso (osimertinib) • Gilotrif (afatinib)
    7ms
    EXCLAIM-2: TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations (clinicaltrials.gov)
    P3, N=354, Active, not recruiting, Takeda | Trial completion date: Jun 2026 --> Dec 2024 | Trial primary completion date: Feb 2026 --> Dec 2024
    Trial completion date • Trial primary completion date • EGFR exon 20
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 20 mutation
    |
    cisplatin • carboplatin • pemetrexed • Exkivity (mobocertinib)
    7ms
    U31402-A-U102: HER3-DXd in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=309, Recruiting, Daiichi Sankyo | Active, not recruiting --> Recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jan 2022 --> Mar 2026
    Enrollment open • Trial completion date • Trial primary completion date • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR L858R • EGFR exon 19 deletion • ALK fusion • EGFR L861Q • ROS1 fusion • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q • ALK-ROS1 fusion
    |
    patritumab deruxtecan (U3-1402)
    8ms
    TREBLE: Aumolertinib With Chemotherapy or Alone Compared With Osimertinib in Patients With Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P3, N=8, Terminated, EQRx International, Inc. | Phase classification: P3b --> P3
    Phase classification • Metastases
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR exon 20 mutation
    |
    cisplatin • Tagrisso (osimertinib) • carboplatin • gemcitabine • albumin-bound paclitaxel • pemetrexed • Ameile (aumolertinib)
    8ms
    Intrathecal Pemetrexed for Leptomeningeal Metastasis in EGFR-Mutant NSCLC (clinicaltrials.gov)
    P2, N=23, Not yet recruiting, Taipei Veterans General Hospital, Taiwan | Trial completion date: May 2025 --> Jun 2027 | Trial primary completion date: May 2025 --> Jun 2026
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib) • pemetrexed
    8ms
    OCEANiC: A Phase II, Open-label, Multi-centre Clinical Trial of Osimertinib With or Without Adjuvant Chemotherapy Guided by Tumour NGS Co-mutation Status and ctDNA Detection in Patients WithnStage IIA-IIIA EGFR-Mutant Non Small Cell Lung Cancer Following Complete Surgical Resection (ACTRN12623000552684)
    P2, N=100, Recruiting, The University of Sydney | Not yet recruiting --> Recruiting
    Enrollment open • Trial initiation date • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib)
    8ms
    Testing the Addition of the Pill Chemotherapy, Cabozantinib, to the Standard Immune Therapy Nivolumab Compared to Standard Chemotherapy for Non-small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2024 --> Sep 2024
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    KRAS G12C • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • ALK rearrangement • EGFR L861Q • ROS1 positive • KRAS G12 • EGFR exon 20 mutation • MET positive • EGFR negative
    |
    Opdivo (nivolumab) • gemcitabine • docetaxel • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Cyramza (ramucirumab) • Cometriq (cabozantinib capsule) • ABP 206 (nivolumab biosimilar)
    9ms
    A Study of NX-019 in Patients With Advanced, Epidermal Growth Factor Receptor (EGFR) Mutant Cancer (clinicaltrials.gov)
    P1, N=258, Recruiting, Nalo Therapeutics Inc. | N=178 --> 258
    Enrollment change • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR L861Q
    |
    NX-019
    9ms
    Unveiling the Landscape of uncommon EGFR Mutations in Non-Small Cell Lung Cancer - A Systematic Review. (PubMed, J Thorac Oncol)
    This systematic review supports the use of 2nd generation TKI afatinib for G719X, S768I, E709X and L747X mutations, as well as for compound uncommon mutations. For other uncommon mutations such as L861Q, 3rd generation TKI, such as osimertinib, could also be considered, given its activity and toxicity profile.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib) • Gilotrif (afatinib)
    10ms
    MET overexpression correlated with prognosis of EGFR-mutant treatment‑naïve advanced lung adenocarcinoma: a real‑world retrospective study. (PubMed, Clin Transl Oncol)
    MET positive expression was an independent predictor of poor outcomes in untreated EGFR L858R mutation advanced LUAD patients treated with first-line EGFR-TKI monotherapy.
    Retrospective data • Journal • Real-world evidence • Real-world • Metastases
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR expression • MET overexpression • EGFR L861Q • EGFR S768I • MET expression • MET positive • EGFR G719A • EGFR G719C
    10ms
    Study to Assess the Effect of AZD9291 on the Blood Levels of Simvastatin in Patients With EGFRm+ NSCLC (clinicaltrials.gov)
    P1, N=52, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    Tagrisso (osimertinib)
    10ms
    Osimertinib and Navitoclax in Treating Patients With EGFR-Positive Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=50, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR positive • EGFR exon 19 deletion + EGFR L861Q
    |
    Tagrisso (osimertinib) • navitoclax (ABT 263)
    11ms
    Current management of uncommon EGFR mutations in non-small cell lung cancer. (PubMed, Curr Probl Cancer)
    It is crucial to understand these distinct variants and their specific responses to active treatment options to optimize care. In this review, we discuss these uncommon mutations in depth and dissect the current literature regarding their treatment outcomes and subsequent evidence-based management guidelines.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 18 mutation
    11ms
    Genomic features of lung cancer patients in Indonesia's national cancer center. (PubMed, BMC Pulm Med)
    EGFR variants are the most found in our centre. Liquid biopsy with ctDNA using NGS examination could detect broad variants and co-variants that will influence the treatment planning.
    Retrospective data • Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    EGFR exon 19 deletion • EGFR wild-type • EGFR L861Q
    11ms
    A Study of ZN-e4 in Subjects With Epidermal Growth Factor Receptor Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=34, Completed, Zeno Pharmaceuticals, Inc. | Phase classification: P1/2 --> P1
    Phase classification • Metastases
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X
    |
    ZN-e4
    11ms
    An Open-Label Phase 1/2 Study of Itacitinib in Combination With Osimertinib in Subjects With Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1/2, N=59, Active, not recruiting, Incyte Corporation | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    Tagrisso (osimertinib) • itacitinib (INCB039110)
    11ms
    AURA: AZD9291 First Time In Patients Ascending Dose Study (clinicaltrials.gov)
    P1/2, N=603, Completed, AstraZeneca | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    Tagrisso (osimertinib)
    1year
    Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=18, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • NOTCH3 (Notch Receptor 3)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib) • tegavivint (BC2059)
    1year
    Comprehensive molecular analysis of driver mutations in non-small cell lung carcinomas and its correlation with PD-L1 expression, An Indian perspective. (PubMed, Pathol Res Pract)
    This is one of the largest cohorts of NSCLC for comprehensive targeted mutational profiling and correlation with the PD-L1 expression. The mutations are more prevalent in non-smoker females for all genes, except ALK (non-smoker males). MET and BRAF mutations are more common in elderly population whereas EGFR mutations, and ALK and ROS1 genes rearrangements are more prevalent in younger population. The most common histopathologic subtype/feature associated with various mutations was as follows: acinar with EGFR, solid with ALK, macronucleoli with ROS1, signet ring with MET, and micropapillary with BRAF.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • ALK rearrangement • MET exon 14 mutation • PD-L1 negative • EGFR L861Q • ALK mutation • ROS1 rearrangement • EGFR G719X • MET mutation • EGFR S768I
    1year
    Treatment of Non-Small Cell Lung Cancer with Atypical EGFR Mutations. (PubMed, Curr Treat Options Oncol)
    Dacomitinib may also be an option for these mutations given similar efficacy to afatinib. Superior CNS penetrance and well managed toxicity profile may also be reasons to consider osimertinib. Given that the choice of TKI may depend on the specific mutation, it is crucial that every patient diagnosed with NSCLC undergo comprehensive sequencing to identify these mutations.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X
    |
    Tagrisso (osimertinib) • Gilotrif (afatinib) • Vizimpro (dacomitinib)
    1year
    AURA2: Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours (clinicaltrials.gov)
    P2, N=210, Completed, AstraZeneca | Active, not recruiting --> Completed
    Trial completion
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    Tagrisso (osimertinib)
    1year
    Balise: A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations (clinicaltrials.gov)
    P2, N=150, Active, not recruiting, Eli Lilly and Company | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q
    |
    erlotinib • emibetuzumab (LY2875358)
    1year
    NCI-2021-04325: Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=55 --> 35
    Enrollment closed • Enrollment change • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    EGFR mutation • BRAF mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q • EGFR T790M negative
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab)
    1year
    Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment (clinicaltrials.gov)
    P1/2, N=45, Terminated, Bridge Biotherapeutics, Inc. | Trial completion date: Jun 2024 --> Nov 2023 | Active, not recruiting --> Terminated; Sponsor's decision considering the changing treatment landscape for NSCLC
    Trial completion date • Trial termination
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q
    |
    BBT-176
    1year
    Prognostic Outcomes and Recurrence Patterns in Resected Stage I Lung Adenocarcinoma Harboring Atypical Epidermal Growth Factor Receptor Mutation. (PubMed, Eur J Cardiothorac Surg)
    Exon20 insertion mutation was correlated with favorable DFS and lower incidence of bone metastasis in radiological solid lung adenocarcinoma harboring atypical EGFR mutation.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L861Q • EGFR G719X • EGFR S768I
    1year
    First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations: The UNICORN Phase 2 Nonrandomized Clinical Trial. (PubMed, JAMA Oncol)
    The results support the use of osimertinib as a treatment option for this patient population. Japan Registry of Clinical Trials Identifier: jRCTs071200002.
    Clinical • P2 data • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib)
    1year
    Comparison and Validation of Rapid Molecular Testing Methods for Theranostic Epidermal Growth Factor Receptor Alterations in Lung Cancer: Idylla versus Digital Droplet PCR. (PubMed, Int J Mol Sci)
    However, considering the prevalence of del19 and L858R in the lung cancer population, the adjusted theranostic values were similar (96.51% and 95.26%, respectively). ddPCR performs better for small specimens and low tumoral content, but in other situations, Idylla is an alternative (especially if a molecular platform is absent).
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR L858R • EGFR exon 19 deletion • EGFR L861Q
    1year
    TARGET: A Phase II, Open-Label, Single-Arm Study of 5-Year Adjuvant Osimertinib in Completely Resected EGFR-Mutated Stage II to IIIB NSCLC Post Complete Surgical Resection. (PubMed, Clin Lung Cancer)
    Exploratory endpoints include: tissue/plasma concordance; analysis of circulating molecules in plasma samples using different profiling approaches to detect minimal residual disease; incidence and change over time of incidental pulmonary nodules. TARGET is currently recruiting, and completion is expected in 2029.
    P2 data • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib)