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Brigatinib: New-generation ALK inhibitor for nonsmall cell lung cancer

Stewart Umbela1, Shahinaz Ghacha1, Revika Matuknauth1

  • 1Lake Erie College of Osteopathic Medicine (LECOM), School of Pharmacy, Bradenton, Florida.

Current Problems in Cancer
|May 22, 2019
PubMed

Insights

Brigatinib is an effective treatment for anaplastic lymphoma kinase-positive metastatic nonsmall cell lung cancer (NSCLC) resistant to crizotinib. The 180 mg dose showed superior efficacy and was well tolerated in clinical trials.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Nonsmall cell lung cancer (NSCLC) is a leading global cause of cancer mortality.
  • Resistance to first-line therapies like crizotinib, a tyrosine kinase inhibitor (TKI), often arises from anaplastic lymphoma kinase (ALK) gene rearrangements.
  • Targeted therapies are crucial for managing advanced NSCLC with specific genetic alterations.

Purpose of the Study:

  • To evaluate the efficacy and tolerability of brigatinib in patients with ALK-positive metastatic NSCLC.
  • To determine the optimal dosing regimen for brigatinib in this patient population.
  • To assess brigatinib as a subsequent therapy option following crizotinib resistance.

Main Methods:

  • Clinical trials were conducted to assess brigatinib's efficacy and safety.
  • Progression-free survival (PFS) was a key endpoint in evaluating treatment effectiveness.
  • Comparative analysis of brigatinib at 180 mg once daily versus 90 mg once daily was performed.

Main Results:

  • Brigatinib demonstrated significant improvement in progression-free survival in patients with crizotinib-resistant ALK-positive metastatic NSCLC.
  • The 180 mg once daily dose of brigatinib exhibited greater efficacy compared to the 90 mg once daily dose.
  • Brigatinib was generally well tolerated, indicating a favorable safety profile.

Conclusions:

  • Brigatinib represents a promising therapeutic option for patients with ALK-positive metastatic NSCLC who have progressed on or are resistant to crizotinib.
  • The 180 mg once daily dose is identified as optimal for maximizing efficacy.
  • Further research is warranted, but current data support brigatinib's role in the treatment landscape of advanced NSCLC.
Keywords:
ALKBrigatinibCrizotinib-resistanceNSCLCTKI

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