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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

Efficacy of Osimertinib in EGFR-Mutated Advanced Non-small-Cell Lung Cancer With Different T790M Status Following

Xiao-Fang Yi¹, Jun Song¹, Ruo-Lin Gao¹

¹Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.

Frontiers in Oncology

|July 5, 2022

Abstract

Purpose:

Epidermal growth factor receptor (EGFR) T790M-negative/unknown advanced non-small cell lung cancer (NSCLC) patients lack subsequent approved targeted therapies. This meta-analysis aimed to assess the efficacy of osimertinib in advanced NSCLC patients with different T790M status after resistance to prior first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and to predict the subgroups that may benefit beside T790M-positive disease.

Methods:

PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant trials. Meeting abstracts were also reviewed to identify appropriate studies. Studies evaluating the efficacy and/or survival outcomes of osimertinib in patients with different T790M status (positive, negative, or unknown) after resistance to prior first- or second-generation EGFR-TKIs were enrolled, and data were pooled to assess hazard ratios (HRs) or relative risk ratios (RRs) in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

Results:

A total of 1,313 EGFR-mutated NSCLC patients from 10 retrospective and one prospective studies treated with osimertinib after resistance to first- or second-generation EGFR-TKIs were included. In overall groups, T790M-positive patients showed an improved OS (HR=0.574, p=0.015), PFS (HR = 0.476, p = 0.017), and ORR (RR = 2.025, p = 0.000) compared with T790M-negative patients. In the brain metastases subgroup, no significant difference in OS was observed between T790M-positive and T790M-negative patients (HR = 0.75, p = 0.449) or between T790M-positive and T790M-unknown patients (HR = 0.90, p = 0.673). In the plasma genotyping subgroup, PFS was similar between T790M-positive and T790M-negative patients (HR = 1.033, p = 0.959).

Conclusion:

Patients with progressive brain metastases on first- or second-generation EGFR-TKIs can benefit from subsequent osimertinib therapy regardless of T790M status. Patients with plasma T790M-negative status and lack of tissue genotyping should be allowed to receive osimertinib treatment.

Insights

Osimertinib shows efficacy in advanced non-small cell lung cancer (NSCLC) patients resistant to prior EGFR-TKIs, regardless of T790M mutation status, especially those with brain metastases. Patients with plasma T790M-negative status may also benefit from this targeted therapy.

Area of Science:

Oncology
Medical Genetics

Background:

Advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) T790M-negative or unknown status lack approved targeted therapies after resistance to first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs).
Identifying effective subsequent treatment strategies is crucial for improving outcomes in this patient population.

Conclusions:

Patients with progressive brain metastases who received first- or second-generation EGFR-TKIs can benefit from subsequent osimertinib therapy irrespective of their T790M mutation status.
Osimertinib treatment should be considered for patients with plasma T790M-negative status, particularly when tissue genotyping is unavailable.

Read full analysis

Keywords:

T790M mutation brain metastases epidermal growth factor receptor non-small cell lung cancer osimertinib

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