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A Bayesian network meta-analysis regarding the comparative efficacy of therapeutics for ALK-positive, brain

Binghao Zhao1, Yan Han1, Yadong Wang2

  • 1Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, PR China.

Pharmacological Research
|October 9, 2021
PubMed

Insights

For ALK-positive brain metastatic non-small cell lung cancer, lorlatinib and alectinib show superior progression-free survival. Alectinib is recommended as a first-line treatment, followed by lorlatinib, particularly upon developing resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • ALK-positive non-small cell lung cancer (NSCLC) with brain metastases (BM) presents unique treatment challenges.
  • Prioritizing interventions for ALK-positive NSCLC with BM requires robust clinical evidence.

Purpose of the Study:

  • To compare the efficacy of various treatments for ALK-positive NSCLC, with a focus on patients with brain metastases.
  • To establish a ranking of interventions based on progression-free survival (PFS), objective response rate (ORR), and overall survival (OS).

Main Methods:

  • A Bayesian network meta-analysis was conducted on data from 11 randomized controlled trials (RCTs) involving 2687 NSCLC patients and 991 with BM.
  • Efficacy outcomes including PFS, ORR, and OS were analyzed using hazard ratios (HR) and odds ratios (OR) with 95% credible intervals (CrIs).

Main Results:

  • For BM patients, lorlatinib, alectinib, and brigatinib demonstrated top-ranking PFS. Brigatinib, lorlatinib, and alectinib were also top-ranked for ORR in BM patients.
  • For all NSCLC patients, lorlatinib, alectinib, and brigatinib ranked highest for PFS. No individual treatment surpassed chemotherapy for OS, though alectinib, lorlatinib, and ceritinib showed promising trends.
  • Lorlatinib exhibited the highest statistical superiority for BM patients, but ORR differences between third- and second-generation inhibitors were not significant.

Conclusions:

  • Alectinib is recommended as the preferred first-line treatment for ALK-positive NSCLC, especially with brain metastases.
  • Lorlatinib is a recommended subsequent treatment option, particularly for patients who develop resistance to alectinib.
  • Further research is needed to analyze subgroup data and adverse events in BM patients.
Keywords:
ALK-positiveBrain metastasisNSCLCNetwork meta-analysis

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