Indirect comparisons of brigatinib and alectinib for front-line ALK-positive non-small-cell lung cancer

Future Oncol. 2022 Jun;18(20):2499-2510. doi: 10.2217/fon-2022-0194. Epub 2022 May 24.

Abstract

Aim: To conduct an indirect treatment comparison (ITC) of the relative efficacy of brigatinib and alectinib for progression-free survival in people with tyrosine kinase inhibitor (TKI)-naive ALK-positive non-small-cell lung cancer (NSCLC). Methods: Final aggregate and patient-level data from the ALTA-1L trial comparing brigatinib to crizotinib and published aggregate data from ALEX (comparing alectinib to crizotinib) were contrasted using Bucher ITC and matching-adjusted indirect comparisons (MAICs). Results: No statistically significant differences were identified between brigatinib and alectinib in reducing the risk of disease progression overall and in patients with baseline central nervous system metastases. Conclusion: Brigatinib appeared similar to alectinib in reducing risk of disease progression for people with TKI-naive ALK-positive NSCLC.

Keywords: ALK inhibitor; Bucher ITC; NSCLC; alectinib; brigatinib; matching-adjusted indirect comparison; progression-free survival; systematic literature review.

Plain language summary

Patients with advanced non-small-cell lung cancer (NSCLC) who have a genetic marker called rearrangement in the anaplastic lymphoma kinase, or ALK-positive disease, are treated with targeted medications taken by mouth. Two medications, alectinib and brigatinib, are both considered first-line treatment for these patients but have not been compared head-to-head. Recently, updated clinical trial results were published for these medications. The present study utilized these updated results and advanced statistical tests to indirectly compare the effectiveness of the two treatments to help guide clinical treatment choices. Results showed brigatinib and alectinib have a similar magnitude of effect in decreasing the risk of a patient with ALK-positive NSCLC developing worsening disease.

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Carbazoles
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Clinical Trials as Topic
  • Crizotinib
  • Disease Progression
  • Humans
  • Lung Neoplasms* / chemically induced
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Organophosphorus Compounds
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines

Substances

  • Carbazoles
  • Organophosphorus Compounds
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Crizotinib
  • Anaplastic Lymphoma Kinase
  • brigatinib
  • alectinib