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Alectinib and Brigatinib: New Second-Generation ALK Inhibitors for the Treatment of Non-Small Cell Lung Cancer

Tyler Beardslee1, Justin Lawson1

  • 1Emory Winship Cancer Institute, Atlanta, Georgia; and Emory University Hospital, Atlanta, Georgia.

Journal of the Advanced Practitioner in Oncology
|December 20, 2018
PubMed

Insights

Second-generation Anaplastic Lymphoma Kinase (ALK) inhibitors like alectinib and brigatinib show promise for non-small cell lung cancer (NSCLC) patients with ALK mutations, offering improved outcomes after crizotinib resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) treatment has advanced with targeted therapies for genetic mutations.
  • Anaplastic Lymphoma Kinase (ALK) mutations occur in ~5% of NSCLC cases.
  • Crizotinib, a first-generation ALK inhibitor, improves outcomes but resistance develops.

Purpose of the Study:

  • To evaluate the efficacy of second-generation ALK inhibitors in ALK-mutated NSCLC.
  • To compare outcomes of newer ALK inhibitors versus traditional chemotherapy and first-generation inhibitors.

Main Methods:

  • Clinical trials comparing ALK inhibitors (crizotinib, ceritinib, alectinib, brigatinib) in first- and second-line settings.
  • Assessment of progression-free survival (PFS) and objective response rate (ORR).

Main Results:

  • Second-generation inhibitors like alectinib and brigatinib demonstrate efficacy in the second-line setting after crizotinib progression.
  • Alectinib showed a 45% ORR and 8-12 month PFS in the second-line setting.
  • Brigatinib demonstrated 45%-54% ORR and 9.2-12.9 month PFS in the second-line setting.
  • Alectinib showed significant PFS benefit over crizotinib in the treatment-naive setting.

Conclusions:

  • Second-generation ALK inhibitors (alectinib, brigatinib) provide effective treatment options for ALK-mutation-positive NSCLC.
  • These newer agents offer improved PFS and response rates, particularly after resistance to first-generation inhibitors.
  • Alectinib demonstrates efficacy in both treatment-naive and second-line settings for ALK-mutated NSCLC.

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