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Bioengineer
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The challenge of overcoming resistance mechanisms in advanced non-small cell lung cancer
- Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has emerged as a cornerstone in treating EGFR-mutated NSCLC.
- However, the inevitable development of resistance mechanisms, such as acquired oncogenic fusions, presents significant hurdles in maintaining long-term therapeutic efficacy.
- Recent insights into the combination of Osimertinib and Selpercatinib offer a promising avenue to address these challenges.
- A case involving an elderly patient with advanced stage IVB EGFR-mutated NSCLC was presented.
- The addition of Selpercatinib, a selective RET inhibitor, to her treatment regimen demonstrated a remarkable clinical benefit, achieving 14 months of progression-free survival.
- RET fusions, although rare, are increasingly recognized as actionable targets in the context of acquired resistance to EGFR-TKIs.
- Selpercatinib’s addition to the therapeutic arsenal marks a significant advance in addressing RET-mediated resistance.
- The combination of Osimertinib and Selpercatinib represents a rational therapeutic strategy to simultaneously target EGFR mutations and RET fusions, providing a dual blockade of critical oncogenic drivers.
- Future directions in managing Osimertinib resistance include the development of sequential and combination regimens tailored to specific resistance mechanisms.
- The durable response achieved with Osimertinib and Selpercatinib underscores the potential of combination therapies to address unmet needs in thoracic oncology.
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