Details

Autor(en) / Beteiligte

• Díaz-Serrano, Asunción
• Gella, Pablo
• Jiménez, Elisabeth
• Zugazagoitia, Jon
• Paz-Ares Rodríguez, Luis

Titel

Targeting EGFR in Lung Cancer: Current Standards and Developments

Ist Teil von

• Drugs (New York, N.Y.), 2018-06, Vol.78 (9), p.893-911

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Lung cancer is the second most common malignant tumor and the leading cause of cancer death. Epidermal growth factor receptor (EGFR) -mutant non-small cell lung cancer (NSCLC) is a distinct subtype of lung cancer comprising approximately 15–40% of non-squamous tumors. The development of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) has been a significant step forward in the treatment of patients with EGFR -mutant tumors, and over the last few years has been the therapy of choice in the initial management of patients with activating mutations in EGFR , with some differences in efficacy and toxicity profile. Up to 50% of patients treated with first- and second-generation TKIs develop an EGFR exon 20 T790M mutation at the time of progression. In this context, osimertinib has shown a great benefit in terms of progression-free survival (PFS) in the second-line setting, including central nervous system metastasis control. The FLAURA trial, which compared osimertinib to first-generation inhibitors as first-line therapy, showed a clear PFS advantage for osimertinib and a trend towards an increased overall survival (OS) assessed by investigator review. Although T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs, other EGFR-dependent and -independent mechanisms have been described, such as HER2 and MET amplifications or BRAF and MEK mutations. Some mechanisms of resistance to osimertinib and other third-generation TKIs have also been described. Several fourth-generation TKIs, targeted drug combinations and immunotherapy strategies are under investigation to overcome resistance to EGFR TKIs in order to improve EGFR -mutant NSCLC patient outcomes.