Non-small cell lung cancer with <i>EGFR</i> exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

Kwon, Christina Soeun; Lin, Huamao Mark; Crossland, Victoria; Churchill, Eric N.; Curran, Eileen A.; Forsythe, A; Tomaras, D.; Ou, Sai‐Hong Ignatius

doi:10.1080/03007995.2022.2083326

Cited by 15 publications

(15 citation statements)

References 61 publications

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“…The third-generation EGFR-TKI osimertinib was approved for the treatment of T790M-mutated NSCLC based on the results of the AURA trial, which was conducted later than the LUX-Lung series [ 19 , 20 ]. Although new drugs, including mobocertinib and amivantamab, have been approved for the treatment of advanced NSCLC with exon 20 insertion mutations, more studies are needed to explore the efficacy of both drugs [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

et al. 2023

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Background Real-world clinical experience with afatinib as a treatment for advanced lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations (G719X, L861Q and S768I) has rarely been reported. Objective We aimed to perform a retrospective multicenter study to analyze afatinib therapy in untreated advanced lung adenocarcinoma harboring uncommon EGFR mutations. Patients and Methods Between May 2014 and June 2021, the data of 90 stage IIIB/IV lung adenocarcinoma patients with uncommon EGFR mutations (G719X/L861Q/S768I) treated with first-line afatinib from the cancer center database of Linkou, Tucheng, and Kaohsiung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results Afatinib had an objective response rate (ORR) of 63.3% and a disease control rate (DCR) of 86.7%. The median progression-free survival (PFS) with first-line afatinib therapy was 17.3 months (95% confidence interval (CI), 12.07-22.53), and the median overall survival (OS) was 28.5 months (95% CI,) in all study patients. In the multivariate analysis, poor performance (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2) and brain and liver metastases were independent predictors of unfavorable PFS. The G719X mutation (alone+compound) was an independent predictor of favorable PFS (hazard ratio (HR) = 0.578; 95% CI, 0.355−0.941; P = 0.027). Most afatinib-related adverse events (AEs) were limited to grades 1 and 2 and were manageable.

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Section: Discussionmentioning

confidence: 99%

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

et al. 2023

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“…In the first-line setting, treatment with platinum doublet chemotherapy leads to a pooled PFS of 5.6 months and a pooled ORR of 24.6%. 14 In a cohort of 57 patients, the ORR was close to 20%, with a PFS of 4.5-5.7 months. 51 Furthermore, a Chinese retrospective analysis indicated that among 104 NSCLC patients who received first-line platinum-based chemotherapy (84.6% received pemetrexed/platinum-based regimens), the ORR was 19.2% and the PFS was 6.4 months.…”

Section: Chemotherapymentioning

confidence: 90%

“…According to a meta-analysis enrolled 8 studies and 206 pooled patients, first-line treatment with EGFR-TKIs resulted in a pooled objective response rate (ORR) of just 6.8% and a pooled progression-free survival (PFS) of 3 months. 14 Relative to classical EGFR mutations, patients with advanced-stage NSCLC harboring EGFRex20ins mutations have considerably shorter PFS (2.9 vs. 10.5 months, p < 0.001) and worse 5-year survival rates (8% vs. 19%) after treatment with first-generation TKIs. 53 While third-generation TKI osimertinib has shown promising efficacy for EGFRex20ins mutations in a small Chinese cohort study (n = 53), another study enrolled 62 Chinese NSCLC patients with different subtypes of EGFRex20ins mutations reported an ORR of only 6.5% and a PFS as short as 2.3 months.…”

Section: Clinical Efficacy Of Conventional Egfr-tki Chemotherapy and ...mentioning

confidence: 94%

“…While driver gene mutations, including the epidermal growth factor receptor (EGFR), have been extensively reported in NSCLC patients, EGFR exon 20 insertions (EGFRex20ins) are the third most frequent type of EGFR mutations, following exon 21 point mutations L858R and exon 19 deletions 2–4 . The majority of patients with EGFRex20ins, in contrast to those with classical EGFR mutations, are highly resistant to current EGFR tyrosine kinase inhibitors (TKIs), classical chemotherapy, and immunotherapy, and their survival is quite unsatisfactory, 5–8 which emphasizes the urgent need for alternative treatment approaches for this subset of patients 3,7,9–14 . In this study, we review the epidemiology, clinicopathological characteristics, detection strategies, and clinical status of EGFRex20ins‐mutant NSCLC patients by aggregating published literature, conference reports, and clinical trial findings.…”

Section: Introductionmentioning

confidence: 99%

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Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non‐small cell lung cancer

Pan,

Liang,

Shi

et al. 2023

Thoracic Cancer

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The third most prevalent type of epidermal growth factor receptor (EGFR) mutation, EGFR exon 20 insertions (EGFRex20ins), involves 2%–12% of all cases of EGFR‐positive non‐small cell lung cancer (NSCLC). Approximately 90% of the mutations occur within the loop structure region, and the most frequently reported subtypes are A767_V769dup and S768_D770dup, which together account for almost 50% of instances. Apart from the unique subtype of A763_Y764insFQEA, NSCLCs with EGFRex20ins are resistant to approved EGFR tyrosine kinase inhibitors (TKIs) and are also insensitive to chemotherapy or immunotherapy. A new modality of treatment for NSCLC patients with EGFRx20ins has been established with the approval of mobocertinib and amivantamab. There are also numerous novel targeted treatments for NSCLC with EGFRex20ins in development, which are anticipated to improve this patient population's survival even further. This review provides a reference for the clinical management of these patients by summarizing the most recent epidemiological, and clinicopathological characteristics, diagnostic techniques, and therapeutic advances of EGFRex20ins in NSCLC.

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“…A novel TKI CLN-081 causes persistent tumor regression in EGFR exon 20ins-driven mouse models [ 20 ]. Early Phase I studies reported a confirmed ORR of 31% [ 52 ]. Data from the ongoing WK-KONG1 and WU-KONG2 studies suggested that sunvozertinib is active in NSCLC pre-treated patients with EGFR Exon20ins, and the ORR is 37.5% [ 53 ].…”

Section: Egfr Activating Mutationsmentioning

confidence: 99%

Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer

Wang

Xing

et al. 2022

Mol Biomed

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Lung cancer is the leading cause of cancer-related mortality worldwide. The discovery of tyrosine kinase inhibitors effectively targeting EGFR mutations in lung cancer patients in 2004 represented the beginning of the precision medicine era for this refractory disease. This great progress benefits from the identification of driver gene mutations, and after that, conventional and new technologies such as NGS further illustrated part of the complex molecular pathways of NSCLC. More targetable driver gene mutation identification in NSCLC patients greatly promoted the development of targeted therapy and provided great help for patient outcomes including significantly improved survival time and quality of life. Herein, we review the literature and ongoing clinical trials of NSCLC targeted therapy to address the molecular pathways and targeted intervention progress in NSCLC. In addition, the mutations in EGFR gene, ALK rearrangements, and KRAS mutations in the main sections, and the less common molecular alterations in MET, HER2, BRAF, ROS1, RET, and NTRK are discussed. The main resistance mechanisms of each targeted oncogene are highlighted to demonstrate the current dilemma of targeted therapy in NSCLC. Moreover, we discuss potential therapies to overcome the challenges of drug resistance. In this review, we manage to display the current landscape of targetable therapeutic patterns in NSCLC in this era of precision medicine.

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Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

Cited by 15 publications

References 61 publications

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

Epidemiological characteristics and therapeutic advances of EGFR exon 20 insertion mutations in non‐small cell lung cancer

Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer

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