AI Article Synopsis
- Chemotherapy, particularly pemetrexed-based regimens, is the primary treatment for advanced non-small-cell lung cancer (NSCLC) patients with specific genetic mutations called EGFR exon 20 insertions (ex20ins), although the research is limited on different subtypes.
- A study analyzed data from 119 patients with EGFR ex20ins, revealing that those treated with pemetrexed had a longer progression-free survival and showed a tendency for better overall survival compared to those who were not treated with it.
- The research suggests that the specific subtype of EGFR ex20ins may influence survival outcomes, with certain subtypes showing a potential advantage, while factors like histological type and bone metastasis are important for prognosis.
Article Abstract
Background: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied.
Methods: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins.
Results: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P<0.05).
Conclusions: To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653161 | PMC |
| http://dx.doi.org/10.21037/tlcr-20-382 | DOI Listing |
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Article Synopsis
- The study focuses on optimizing inhibitors for epidermal growth factor receptor (EGFR) Exon20 insertions (Ex20Ins) using structure-based drug design (SBDD).
- A new compound was discovered that is both effective against EGFR Ex20Ins and able to cross the blood-brain barrier in preclinical tests.
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[EGFR Exon 20 Insertion Mutation: Research Status and New Treatment Strategies].
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August 2024
Department of Respiratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital 
Affiliated to Shanxi Medical University, Taiyuan 030013, China.
In non-small cell lung cancer (NSCLC), as an improtant oncogenic driver gene, epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) has a unique protein structure and is primarily drug-resistant to traditional EGFR-tyrosine kinase inhibitors (EGFR-TKIs). In recent years, exploration of targeted therapy for EGFR ex20ins has never stopped. Firstly Mobocertinib and Amivantamab obtained approval from U.
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