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EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non-Small Cell Lung Cancer - PubMed

EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non-Small Cell Lung Cancer - PubMed

Source : https://pubmed.ncbi.nlm.nih.gov/34127383/

Although phenotypically similar to patients with common EGFR mutations, patients with EGFR ex20-mut had worse survival, perhaps due to the lack of targeted therapies. Chemotherapy was superior to conventional EGFR TKIs in patients with EGFR ex20-ins, although there was moderate activity of TKIs in S ...

  • June 22, 2021

    Key Points
    • In the current retrospective study, 109 Australian patients with NSCLC harboring epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) (excluding T790M) were assessed for clinical characteristics and treatment outcomes.
    • The authors wrote, “Our data reaffirm that platinum-based chemotherapy has superior activity compared with conventional EGFR TKIs in ex20-ins and confirm the moderate activity of such TKIs in patients with S768I exon 20 mutations, in addition to revealing the lack of effectivity of ICI monotherapy. Phenotypically, these patients were very similar to those with activating mutations; however, survival was inferior, likely due to limited availability to specific targeted agents during recruitment.”
    • They added, “Although targeted therapy success has yet to be realized in this subset, several promising agents are emerging targeting the unique, complex, and heterogeneous EGFR exon 20 oncogene. Ultimately, it is hoped that these agents will alter the clinical course of this disease and shift the paradigm from cytotoxic chemotherapy to a new frontier of targeted therapies.”
    • The authors noted that their preliminary analysis indicated that the clinical characteristics of patients with ex20-ins are similar to common EGFR, but the prognosis is worse and akin to the EGFR wild-type population. Response to ICI therapy needs to be elucidated.
    • One limitation of the current study was its use of different platforms such as PCR and next-generation sequencing based on its retrospective nature. Consequently, patients in this cohort may not reflect the full gamut of advanced NSCLC and EGFR exon 20 insertion mutations. Furthermore, there was non-centralized analysis of scans and tumor evaluations at regular intervals, which could have affected ORR, PFS, and OS. In particular, cases of healthier patients administered first-line chemotherapy who lived longer could have served as a source of selection bias.