EGFR-Directed Therapy in Lung Cancer

This Element describes the pathophysiology and current and future management of EGFR-mutant non-small cell lung cancer.

So Yeon Kim (Author), Daniel B. Costa (Author), Daisuke Shibahara (Author), Susumu Kobayashi (Author), Balazs Halmos (Author)

9781009342308, Cambridge University Press

Paperback / softback, published 26 January 2023

75 pages
22.8 x 15.2 x 0.3 cm, 0.08 kg

Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a clinically important driver alteration affecting approximately one-third of lung cancer patients. Treatments for EGFR-exon 19 deletion and exon 21 L858R NSCLC have evolved over the last decade from first-generation reversible tyrosine kinase inhibitors (TKI) to third-generation irreversible TKIs, of which osimertinib has been the widely accepted as first-line therapy. Despite survival improvement seen with osimertinib and its efficacy against acquired T790M mutation, resistance through on-target and off-target pathways eventually develop. This Element describes the structural biology and pathophysiology of EGFR-mutant NSCLC and discusses past, current, and future treatment options in the metastatic, neoadjuvant, and adjuvant settings. It describes the biology and recently approved treatment for EGFR-exon 20 insertion mutation and the treatment for the uncommon exon 18 (G719X), 20 (S768I), and 21 (L861Q) mutations. It also outlines the promising clinical applications of circulating tumor DNA (ctDNA).

1.Structural biology and mechanism of activation of EGFR
2. EGFR-associated oncogenesis
3. Tyrosine kinase inhibitors (TKIs) as targeted treatment for EGFR-mutant NSCLC
4. EGFR-TKIs as adjuvant or neoadjuvant therapy
5. EGFR-Exon 20 insertion mutations
6. Resistance mechanisms and therapies in metastatic resistant EGFR-NSCLC
7. Uncommon EGFR-activating mutations
8. Immunotherapy in metastatic EGFR-mutant NSCLC
9. Management of CNS disease and oligometastatic EGFR-mutant NSCLC
10. ctDNA in EGFR-mutant NSCLC
11. Guidelines and recommendations for EGFR-mutant NSCLC
References.

Subject Areas: Respiratory medicine [MJL], Oncology [MJCL], Medical diagnosis [MJA]