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Ceritinib as a promising therapy for ALK related diseases

Monica Ceccon1

  • 1Department of Health Science, University of Milano Bicocca, Monza, Italy.

Translational Lung Cancer Research
|March 26, 2015
PubMed

Insights

Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor showing promise in treating ALK-positive non-small cell lung cancer, even after resistance to crizotinib. Further research is needed to optimize its use due to adverse events.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Anaplastic lymphoma kinase (ALK) inhibitors are crucial for treating specific cancers like non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma (ALCL).
  • Crizotinib, a first-generation ALK inhibitor, demonstrated efficacy but resistance necessitates the development of new therapeutic agents.
  • Emergence of resistance to crizotinib highlights the need for next-generation ALK inhibitors to improve patient outcomes.

Purpose of the Study:

  • To evaluate the clinical efficacy and safety of ceritinib, a second-generation ALK inhibitor.
  • To assess ceritinib's potential as a treatment option for patients with ALK-positive malignancies, particularly those who have progressed on crizotinib.
  • To compare ceritinib's performance against other ALK inhibitors like crizotinib and alectinib.

Main Methods:

  • Phase I clinical trial involving dose-escalation and expansion phases.
  • Enrollment of 130 patients (59 in dose-escalation, 71 in expansion).
  • Evaluation of efficacy in 19 patients with crizotinib-resistant disease, assessing overall response rate (ORR) and progression-free survival (PFS).

Main Results:

  • Ceritinib demonstrated an overall response rate (ORR) of 58% in patients treated, with 56% response in those previously treated with crizotinib.
  • The maximum tolerated dose (MTD) was determined to be 750 mg daily.
  • Over half of the patients required dose reduction due to adverse events, with a progression-free survival (PFS) of 7.0 months.

Conclusions:

  • Ceritinib shows significant activity in ALK-positive NSCLC, including in patients resistant to crizotinib.
  • Adverse events necessitate careful dose management, indicating a need for further optimization.
  • Ceritinib represents a viable second-generation ALK inhibitor, warranting comparison with other agents like alectinib.
Keywords:
Anaplastic lymphoma kinase (ALK)crizotinibdrug resistancenon-small cell lung cancer (NSCLC)

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