Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer.

ABSTRACT:

Purpose

Alectinib is a selective and potent anaplastic lymphoma kinase (ALK) inhibitor that is active in the central nervous system (CNS). Alectinib demonstrated robust efficacy in a pooled analysis of two single-arm, open-label phase II studies (NP28673, NCT01801111; NP28761, NCT01871805) in crizotinib-resistant ALK-positive non-small-cell lung cancer (NSCLC): median overall survival (OS) 29.1 months (95% confidence interval [CI]: 21.3-39.0) for alectinib 600 mg twice daily (BID). We investigated exposure-response relationships from final pooled phase II OS and safety data to assess alectinib dose selection.

Methods

A semi-parametric Cox proportional hazards model analyzed relationships between individual median observed steady-state trough concentrations (C_trough,ss</

SUBMITTER: Morcos PN 

PROVIDER: S-EPMC6010493 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature