ArticleClinical and translational science2022
Population pharmacokinetic and exposure-response analyses from ALTA-1L: Model-based analyses supporting the brigatinib dose in ALK-positive NSCLC.
Article in Clinical and translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- HPLC-MS Quantification of Multiple Tyrosine Kinase Inhibitors in Patients with Solid Tumors: Method Validation and Clinical Application.Pharmaceutics · 2026Article
- Therapeutic Drug Monitoring and Model-Informed Precision Dosing of Oral TKIs and PARP Inhibitors: A Practical Framework for Clinical Implementation.Clinical pharmacokinetics · 2026Review
- [Expert Consensus on Rational Use and Monitoring of Small Molecule Targeted Drugs for Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology.Clinical pharmacokinetics · 2023Review
- Clinical Pharmacology of Brigatinib: A Next-Generation Anaplastic Lymphoma Kinase Inhibitor.Clinical pharmacokinetics · 2023Review
- Brigatinib pharmacokinetics in patients with chronic hepatic impairment.Investigational new drugs · 2023Article
- Population pharmacokinetic and exposure-response analyses from ALTA-1L: Model-based analyses supporting the brigatinib dose in ALK-positive NSCLC.Clinical and translational science · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ALK in Lung Cancer Trial of brigAtinib in First Line (ALTA-1L) compared brigatinib versus crizotinib in anaplastic lymphoma kinase (ALK) inhibitor-naive patients with ALK+ non-small cell lung cancer (NSCLC). A population pharmacokinetic (PK) model was used to estimate brigatinib exposures for exposure-efficacy and exposure-safety analyses in ALTA-1L. A previously developed population PK model for brigatinib was applied to estimate brigatinib PK parameters. Relationships between static (time-independent) and dynamic (time-varying) exposure metrics and efficacy (progression-free survival [PFS], objective response rate [ORR], and intracranial ORR [iORR]) and safety outcomes (selected grade ≥2 and grade ≥3 adverse events [AEs]) were evaluated using logistic regression and time-to-event analyses. There were no meaningful differences in brigatinib PK in the first-line and second-line settings, supporting use of the previous population PK model for the first-line population. Exposure-response analyses showed no significant effect of time-varying brigatinib exposure on PFS. Brigatinib exposure was not significantly related to ORR, but higher exposure was associated with higher iORR (odds ratio: 1.13, 95% confidence interval: 1.01-1.28, p = 0.049). Across the observed median exposure (5th-95th percentile) at steady state for 180 mg once daily, the predicted probability of iORR was 0.83 (0.58-0.99). AEs significantly associated with higher exposure were elevated lipase (grade ≥3) and amylase (grade ≥2). Time to first brigatinib dose reduction was not related to exposure. These results support the benefit-risk profile of first-line brigatinib 180 mg once daily (7-day lead-in dose at 90 mg once daily) in patients with ALK+ NSCLC.
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