Details

Autor(en) / Beteiligte

• Lai-Kwon, Julia
• Tiu, Crescens
• Pal, Abhijit
• Khurana, Sachin
• Minchom, Anna

Titel

Moving beyond epidermal growth factor receptor resistance in metastatic non-small cell lung cancer - a drug development perspective

Ist Teil von

• Critical reviews in oncology/hematology, 2021-03, Vol.159, p.103225-103225, Article 103225

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •EGFR mutations are the most common actionable driver mutation in metastatic non-small cell lung cancer (NSCLC).•EGFR-targeting tyrosine kinase inhibitors have high response rates but acquired resistance is common.•Novel drugs targeting key drivers of resistance are in preclinical and clinical development.•Drug combinations has been investigated but none have achieved licensing approval.•Access to ctDNA/ next generation sequencing is needed to identify rare molecular patient sub-populations. Epidermal Growth Factor Receptor (EGFR) mutations are the most common targetable oncogenic driver mutation in metastatic non-small lung cancer (NSCLC). There have been significant advances in the management of metastatic EGFR-mutant NSCLC from the advent of first and second generation EGFR inhibitors to, more recently, the third-generation inhibitor osimertinib. Osimeritinib is now established as first-line therapy on the basis of improved outcomes compared to first and second generation agents. However, despite excellent initial response rates, responses may not be durable due to the development of acquired resistance. Understanding these mechanisms of resistance is critical to the development of rational drug and drug combinations capable of circumventing them. We discuss the major mechanisms of resistance to first, second and third generation EGFR TKIs. The potential of drug combinations utilising chemotherapy, immunotherapy and anti-angiogenic drugs are explored. We examine strategies to aid drug development, including circulating tumour DNA and novel trial designs.