Management of ceritinib therapy and adverse events in patients with ALK-rearranged non-small cell lung cancer

Lung Cancer. 2017 Sep:111:51-58. doi: 10.1016/j.lungcan.2017.06.004. Epub 2017 Jun 9.

Abstract

Anaplastic lymphoma kinase rearrangement (ALK+) occurs in approximately 2-7% of patients with non-small cell lung cancer (NSCLC), contributing to a considerable number of patients with ALK+ NSCLC worldwide. Ceritinib is a next generation ALK inhibitor (ALKi), approved by the European Medicines Agency in 2015. In the first-in-human, phase I study, ceritinib demonstrated rapid and durable responses in ALK patients previously treated with a different ALKi and in those who were ALKi-naive. As ceritinib is starting to be used routinely for the treatment of patients with ALK+ NSCLC, experience is growing with regard to ideal therapy management. In this review we provide a brief background to the development of ceritinib. The optimal treatment management and adverse events associated with ceritinib in clinical trials and in clinical practice are then discussed in detail, and where applicable, an expert consensus on specific recommendations are made. In clinical trials, the most common adverse events related to ceritinib are nausea, vomiting, and diarrhea. However, the majority of these are mild and, in the opinion of the authors, can be effectively managed with dose modifications. Based on clinical data, ceritinib has demonstrated efficacy as a first-line therapy and in patients who have relapsed on crizotinib, including those with brain metastases at baseline. Unfortunately, at some point, all patients experience progressive disease, with the central nervous system being a common site of metastases. Recommendations are made for continuing treatment beyond disease progression as long as a clinical benefit to patients is observed. Here, we review management of ceritinib treatment and adverse events and make recommendations on optimal management of patients.

Keywords: Anaplastic lymphoma kinase; Ceritinib; Non-small cell lung cancer; Safety profile; Therapy management.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / secondary
  • Brain Neoplasms / therapy
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Management
  • Disease Progression
  • Drug Interactions
  • Drug Resistance, Neoplasm
  • Follow-Up Studies
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Molecular Targeted Therapy
  • Oncogene Proteins, Fusion / genetics*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Sulfones / administration & dosage
  • Sulfones / adverse effects
  • Sulfones / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Sulfones
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • ceritinib