Journal: Chinese medical journal
This systematic review traces nearly three decades of development of EGFR-targeted therapy in NSCLC, focusing on how successive generations of EGFR tyrosine kinase inhibitors have reshaped management of EGFR‑mutant disease.
Key points:
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Therapeutic evolution:
The review outlines progression from:
- First‑generation reversible TKIs (gefitinib, erlotinib, icotinib)
- Second‑generation irreversible pan‑HER TKIs (afatinib, dacomitinib)
- Third‑generation, mutation‑selective TKIs (e.g., osimertinib, aumolertinib, furmonertinib, befotertinib, rezivertinib, rilertinib, limertinib, lazertinib, mifanertinib) targeting sensitizing mutations and T790M
- Newer context-specific agents, including sunvozertinib for exon 20 insertions and zorifertinib for patients with brain metastases
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Expansion across the disease continuum:
EGFR-TKIs have moved from use solely in advanced/metastatic settings to broader roles, including:
- Perioperative settings (neoadjuvant/adjuvant)
- Maintenance and longer‑term disease control strategies
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Combination strategies:
The review summarizes how combining EGFR-TKIs with other modalities has expanded treatment options and contributed to improvements in survival and quality of life, including combinations with:
- Chemotherapy
- Anti‑angiogenic therapy
- Other targeted approaches
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Ongoing challenges:
Despite major gains, acquired resistance remains a central barrier to durable control. The article discusses known resistance mechanisms and the need for next‑generation agents and rational combinations to overcome them.
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Future directions:
The authors highlight emerging therapies and anticipated developments through 2026, emphasizing:
- Continued personalization of treatment
- Better management of CNS disease
- Strategies to delay or circumvent resistance
Overall, the publication provides a historical and forward-looking overview of EGFR-TKI therapy in NSCLC, underscoring its transformation into a foundational component of care for EGFR‑mutant disease while identifying resistance and long‑term disease control as the key remaining unmet needs.