Related Experiment Video
Updated: Jun 6, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
[More Personalized Treatment using Diversified Molecular Targeted Therapy Strategies for EGFR Mutation-Positive
Nobuhiko Seki1, Hiroshige Yoshioka, Satoshi Wakabayashi
1Division of Medical Oncology, Dept. of Internal Medicine, Teikyo University School of Medicine.
Abstract:
For epidermal growth factor receptor(EGFR)gene mutation-positive advanced non-small-cell lung cancer, molecular targeted therapy with EGFR tyrosine kinase inhibitors(EGFR-TKIs)is the mainstay of treatment. In Japan, 5 EGFR-TKIs[gefitinib and erlotinib(first-generation), afatinib and dacomitinib(second-generation), and osimertinib(third-generation)]have been approved, and only ramucirumab, an anti-angiogenic agent, has been approved for use in combination with the first-generation EGFR-TKIs. Since only osimertinib is approved for use in second-line therapy in the patients with confirmed T790M mutation after EGFR-TKI treatment, any other EGFR-TKI than osimertinib has to be selected as the first-line therapy of sequential treatment using EGFR-TKIs both as first-line and second-line therapy. Treatment options vary widely, and it is therefore important to select an optimal treatment based on clinical information such as a subtype of the EGFR gene mutation, as well as the patient's preference to potentially use molecular targeted therapy for second-line therapy. This article outlines clinical study data on the use of EGFR-TKIs as first- and second-line therapies and the use in combination with anti-angiogenic agents. It also describes our clinical experience with a successful shift from first-line therapy with an EGFR-TKI to second-line therapy with EGFR-TKI in sequential treatment.
Insights
Optimizing epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy for advanced non-small-cell lung cancer is crucial. Selecting the right EGFR-TKI sequence, considering mutation subtypes and patient preference, improves treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Advanced non-small-cell lung cancer (NSCLC) with EGFR mutations is primarily treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs).
- Japan has approved five EGFR-TKIs (gefitinib, erlotinib, afatinib, dacomitinib, osimertinib) and one anti-angiogenic agent (ramucirumab) for specific NSCLC treatment scenarios.
- Osimertinib is the only approved second-line therapy for T790M-positive NSCLC post-EGFR-TKI treatment, necessitating careful first-line selection for sequential therapy.
Purpose:
- To review clinical study data on first- and second-line EGFR-TKI therapies and combination treatments with anti-angiogenic agents.
- To discuss the selection of optimal EGFR-TKI treatment strategies based on EGFR mutation subtypes and patient preferences for sequential therapy.
- To present clinical experience with successful sequential EGFR-TKI treatment in advanced NSCLC.
Summary:
- The mainstay of treatment for EGFR mutation-positive advanced non-small-cell lung cancer is molecular targeted therapy with EGFR tyrosine kinase inhibitors (EGFR-TKIs).
- Treatment options are diverse, requiring careful selection of first-line EGFR-TKIs based on mutation status and patient preference for subsequent therapies, especially since osimertinib is the sole approved second-line option for T790M mutations.
- This review covers clinical data on EGFR-TKI monotherapies and combination regimens, alongside a case study of successful sequential EGFR-TKI treatment.
Impact:
- Provides a comprehensive overview of EGFR-TKI treatment strategies in advanced NSCLC, aiding clinicians in optimizing patient care.
- Highlights the importance of personalized treatment selection based on molecular profiling and patient factors for improved therapeutic efficacy.
- Offers insights into sequential EGFR-TKI therapy, including successful clinical transitions, to guide future treatment protocols.
More Related Videos
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:38Mitogens and the Cell Cycle
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...