Ceritinib: an orphan drug for ALK positive non-small cell lung cancer with robust clinical evidence Article

Rolfo, C, Arias, D, Gandia, JF et al. (2017). Ceritinib: an orphan drug for ALK positive non-small cell lung cancer with robust clinical evidence . 5(12), 991-997. 10.1080/21678707.2017.1406347

cited authors

  • Rolfo, C; Arias, D; Gandia, JF; Manca, P; Santos, E; Raez, LE

authors

abstract

  • Introduction: Crizotinib is approved for the first line treatment in ALK+ lung adenocarcinomas due to the results of the PROFILE 1001 and PROFILE 1005 trials. Unfortunately, as in all targeted therapies, patients will inevitably experience disease progression over time. Mechanisms of resistance to ALK inhibitors include gatekeeper mutations (L1196M and G1269A), increase the number of copies of the fusion gene and the development of alternative routes to ALK, like EGFR, KRAS, cKIT, among others. Areas covered: Second generation ALK inhibitors are a new option. ASCEND 4 compared ceritinib vs chemotherapy in first line and ASCEND 5 ceritinib vs chemotherapy in second line after receiving Crizotinib, both with a significant benefit in PFS with an interesting HR (<0.5). This drug also crosses the blood-brain barrier and induces responses in brain metastases (ORR 72%) with a good safety and tolerability profile. Expert opinion: Ceritinib demonstrated a robust activity in intra and extra cranial disease. There are other second generation TKIs approved (in Japan and USA) like alectinib, which demonstrated also a strong activity in this subpopulation of NSCLC; brigatinib, recently approved in USA, lorlatinib and other compounds that are new members of this continuous growing family of TKI, making this field a very exciting topic in lung cancer.

publication date

  • December 2, 2017

Digital Object Identifier (DOI)

start page

  • 991

end page

  • 997

volume

  • 5

issue

  • 12