Moving beyond epidermal growth factor receptor resistance in metastatic non-small cell lung cancer - a drug development perspective.
Crit Rev Oncol Hematol
; 159: 103225, 2021 Mar.
Article
en En
| MEDLINE
| ID: mdl-33482349
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Crit Rev Oncol Hematol
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido