Brigatinib and Alectinib for ALK Rearrangement-Positive Advanced Non-Small Cell Lung Cancer With or Without Central...

Area of Science:

• Oncology
• Pharmacology
• Biostatistics

Background:

• Anaplastic lymphoma kinase (ALK) rearrangement-positive non-small cell lung cancer (NSCLC) is a distinct subtype.
• Brigatinib and alectinib are targeted therapies for ALK-positive NSCLC, but direct comparative efficacy data, especially with central nervous system (CNS) metastasis, is lacking.

Purpose of the Study:

• To indirectly compare the efficacy of brigatinib and alectinib in ALK-inhibitor-naïve, advanced NSCLC patients with and without CNS metastasis.
• To rank the efficacy of these treatments using Surface Under the Cumulative Ranking (SUCRA) values.

Main Methods:

• An indirect treatment comparison (ITC) using a Bayesian model with crizotinib as a common comparator.
• Progression-free survival (PFS) was the primary efficacy endpoint.
• Analysis of adverse events (G3-5) was also performed.

Main Results:

• No significant difference in PFS was observed between brigatinib and alectinib in the overall patient population.
• Alectinib demonstrated the highest efficacy ranking in the overall population, whereas brigatinib showed a higher ranking in the subgroup with CNS metastasis.
• No significant difference in severe adverse events (G3-5) was found between the two drugs in the overall population; data for the CNS subgroup was insufficient.

Conclusions:

• Brigatinib and alectinib exhibit comparable efficacy in terms of PFS for advanced ALK-positive NSCLC.
• Treatment choice may depend on the presence of CNS metastasis, with brigatinib potentially offering an advantage in this subgroup.
• Further randomized controlled trials are necessary to validate these findings.