Trial reportCPT: pharmacometrics & systems pharmacology2020
Brigatinib Dose Rationale in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: Exposure-Response Analyses of Pivotal ALTA Study.
Trial report in CPT: pharmacometrics & systems pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Mobocertinib Dose Rationale in Patients with Metastatic NSCLC with EGFR Exon 20 Insertions: Exposure-Response Analyses of a Pivotal Phase I/II Study.Clinical pharmacology and therapeutics · 2022Trial
- Serum creatine kinase elevation following tyrosine kinase inhibitor treatment in cancer patients: Symptoms, mechanism, and clinical management.Clinical and translational science · 2024Review
- Evaluation of the drug-drug interaction potential of brigatinib using a physiologically-based pharmacokinetic modeling approach.CPT: pharmacometrics & systems pharmacology · 2024Article
- Brigatinib treatment in a patient with advanced NSCLC with XPO1-ALK fusion: a case report.Frontiers in oncology · 2024Article
- Brigatinib pharmacokinetics in patients with chronic hepatic impairment.Investigational new drugs · 2023Article
- Concentration QTc analysis of giredestrant: Overcoming QT/heart rate confounding in the presence of drug-induced heart rate changes.Clinical and translational science · 2023Article
- [Early Onset Pulmonary Events and Management Strategies during the Treatment of ALK Positive NSCLC Patients with Brigatinib].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Finding the right hazard function for time-to-event modeling: A tutorial and Shiny application.CPT: pharmacometrics & systems pharmacology · 2022Article
- Pharmacometric analyses and clinical evidence for brigatinib dosing in anaplastic lymphoma kinase-positive non-small cell lung cancer.British journal of clinical pharmacology · 2022Article
- 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
- Pharmacokinetically-guided dosing to improve the efficacy of brigatinib in non-small cell lung cancer patients.British journal of clinical pharmacology · 2022Article
- Safety profile of tyrosine kinase inhibitors used in non-small-cell lung cancer: An analysis from the Italian pharmacovigilance database.Frontiers in oncology · 2022Article
- Review
- Effect of severe renal impairment on the pharmacokinetics of brigatinib.Investigational new drugs · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brigatinib is a kinase inhibitor indicated for patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer who progressed on or are intolerant to crizotinib. Approval was based on results from a randomized, dose-ranging phase II study (ALK in Lung Cancer Trial of AP26113 (ALTA)). Despite an apparent dose-response relationship for efficacy in ALTA, an exposure-response relationship was not discernable using static models driven by time-averaged exposure. However, exposure-response modeling using daily time-varying area under the concentration curve as the predictor in time-to-event models predicted that increasing the dose of brigatinib (range, 30 mg once daily (q.d.) to 240 mg q.d.) would result in clinically meaningful improvements in progression-free survival (PFS), intracranial PFS, and overall survival. Grade ≥ 2 rash and amylase elevation were predicted to significantly increase with brigatinib exposure. These results provided support for a favorable benefit-risk profile with the approved dosing regimen (180 mg q.d. with 7-day lead-in at 90 mg) versus 90 mg q.d.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.