Trial reportThe AAPS journal2014
Lower exposure and faster clearance of bevacizumab in gastric cancer and the impact of patient variables: analysis of individual data from AVAGAST phase III trial.
Trial report in The AAPS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05640609 (A Phase Ib/II Trial of Capeox Regimen Combined With Sintilimab and Bevacizumab in First-line Treatment for Recurrent or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma), which is not on this map. Cited by 18 papers.
What it found
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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.
A Phase Ib/II Trial of Capeox Regimen Combined With Sintilimab and Bevacizumab in First-line Treatment for Recurrent or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma
Who cites it
18 citing papers in PubMed, 48 citations in OpenAlex.
- Pharmacokinetics of the Monoclonal Antibody MHAA4549A Administered in Combination With Oseltamivir in Patients Hospitalized With Severe Influenza A Infection.Journal of clinical pharmacology · 2020Trial
- Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer.Cancer chemotherapy and pharmacology · 2019Trial
- Sex as a Biological Variable in Early-Phase Oncology Clinical Trials: Enhancing the Path to Personalised Medicine.Heliyon · 2024Review
- Antibody Drug Clearance: An Underexplored Marker of Outcomes with Checkpoint Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Pharmacokinetics of biologics in gastric cancer.Clinical and translational science · 2023Review
- Population pharmacokinetics of zanidatamab, an anti-HER2 biparatopic antibody, in patients with advanced or metastatic cancer.Cancer chemotherapy and pharmacology · 2022Article
- Precision Medicine: A New Paradigm in Therapeutics.International journal of preventive medicine · 2021Review
- Direct and Precise Measurement of Bevacizumab Levels in Human Plasma Based on Controlled Methionine Oxidation and Multiple Reaction Monitoring.ACS pharmacology & translational science · 2020Article
- Correlation Between Bevacizumab Exposure and Survival Does Not Necessarily Imply Causality.The oncologist · 2020Article
- Galectin-1 promotes vasculogenic mimicry in gastric adenocarcinoma via the Hedgehog/GLI signaling pathway.Aging · 2020Article
- Understanding Inter-Individual Variability in Monoclonal Antibody Disposition.Antibodies (Basel, Switzerland) · 2019Review
- A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors.Investigational new drugs · 2019Article
- Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer.International journal of oncology · 2019Article
- Population pharmacokinetic and covariate analyses of intravenous trastuzumab (HerceptinCancer chemotherapy and pharmacology · 2019Article
- Investigation of the Influence of Protein-Losing Enteropathy on Monoclonal Antibody Pharmacokinetics in Mice.The AAPS journal · 2017Article
- Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.Cancer chemotherapy and pharmacology · 2017Article
- Inhibitory effects of bevacizumab monoclonal antibodies in combination with chemotherapy in different time sequences on a human gastric carcinoma cell line.Irish journal of medical science · 2017Article
- Population pharmacokinetics of bevacizumab in cancer patients with external validation.Cancer chemotherapy and pharmacology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Altered pharmacokinetics of antibody drugs has been reported in advanced gastric cancer (AGC). We aim to evaluate bevacizumab pharmacokinetics in AGC from the Phase III trial (AVAGAST), and explore the influence of patient variables. Bevacizumab concentrations (Cp) were measured in plasma samples taken following disease progression from 162 patients (7.5 mg/kg every 3 weeks). Predicted Cp [median and 90% prediction interval] was simulated using the population pharmacokinetic model established for other cancers (PPK model) and compared to observed Cp. Bevacizumab clearance was estimated using NONMEM and compared between subgroups. Patient characteristics of AGC are similar to other cancers except for lower body weight despite higher percentage of males. Eighty-five percent of observed Cp was below the median predicted Cp and 38% below the lower boundary of the 90% prediction interval. Median bevacizumab clearance in AGC was 4.5 versus 3 mL/day/kg in other cancers. Bevacizumab clearance was significantly faster (p < 0.05) in patients without gastrectomy (n = 42) or lower albumin. Clearance appeared to be faster in patients with lower total protein, higher ECOG scores, more metastatic sites, and poorer response. No significant difference in bevacizumab concentrations and clearance was observed between Asian and Non-Asian patients. AGC patients exhibited significantly lower bevacizumab exposure due to an approximate 50% increase in clearance versus other cancers. Bevacizumab is cleared faster in patients without prior gastrectomy. No significant difference in bevacizumab pharmacokinetics was observed between Asian and Non-Asian patients. The underlying mechanism for faster bevacizumab clearance in AGC is unknown and warrants further research.
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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.