First-line treatments for patients with advanced ALK gene rearrangements in NSCLC: a systematic review and network

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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

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Jiahao Tao1,2, Chuangjie Zheng1,2, Cuifen Zhang1,2

  • 1Cancer Centre, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

The Journal of International Medical Research
|November 16, 2022
PubMed
Abstract

Insights

Lorlatinib shows the best progression-free survival (PFS) for ALK-positive non-small cell lung cancer (NSCLC), especially for patients with brain metastases. Brigatinib is optimal for Asian patients, while alectinib offers the greatest survival advantage.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • Non-small cell lung cancer (NSCLC) with an Anaplastic Lymphoma Kinase (ALK) gene rearrangement requires targeted therapy.
  • First-line treatment selection for ALK-positive NSCLC impacts patient outcomes.
  • Optimizing first-line ALK inhibitor therapy is crucial for improving progression-free survival (PFS) and overall survival.

Approach:

  • A Bayesian network meta-analysis was performed on nine randomized controlled trials.
  • Included trials focused on first-line ALK inhibitors for ALK-positive NSCLC patients.
  • Efficacy (PFS, objective response) and safety (adverse events) were evaluated.

Key Points:

  • Lorlatinib demonstrated superior PFS compared to brigatinib (HR 0.79).
  • Lorlatinib showed the highest probability for best PFS in patients with or without brain metastases.
  • Brigatinib had the highest PFS probability among Asian patients.
  • Alectinib offered the highest survival advantage probability (57%).
  • Lorlatinib had the highest probability for objective response (41%).
  • Alectinib had the highest probability of being ranked lowest for severe adverse events (86%).

Conclusions:

  • Lorlatinib is the optimal first-line therapy for ALK-positive NSCLC, particularly for patients with brain metastases.
  • Brigatinib is the preferred first-line option for Asian patients with ALK-positive NSCLC.
  • Treatment choice should consider PFS, survival advantage, response rates, and safety profiles.
Keywords:
ALK inhibitorsNon-small cell lung canceranaplastic lymphoma kinasebrigatinibfirst-line therapylorlatinib

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