Trial reportJournal of clinical pharmacology2022
Pharmacokinetic Simulation Analysis of Less Frequent Nivolumab and Pembrolizumab Dosing: Pharmacoeconomic Rationale for Dose Deescalation.
Trial report in Journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed.
- REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers.Contemporary clinical trials · 2023Trial
- Dosing, duration, and timing controversies in determining immune checkpoint inhibitor dosing regimens.NPJ precision oncology · 2026Article
- Model-Based Alternative Dosing Strategies for Subcutaneous Nivolumab to Improve Cost Effectiveness.Clinical pharmacokinetics · 2026Article
- Immunotherapeutic potential of PD-1 blockade in chronic Leishmania mexicana infection through the enhancement of progenitor-like CXCR5Frontiers in immunology · 2026Article
- The combination of body mass index and serum creatinine levels predicts survival in patients with Hodgkin lymphoma treated with nivolumab in the CheckMate 205 study.Oncoimmunology · 2025Article
- A Systematic Evaluation of the Dosing Regimens for Approved Targeted Therapies and Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma From a Project OPTIMUS Perspective.Journal of clinical pharmacology · 2025Review
- Totality of the Evidence: Optimizing Dosage Selection Strategies in Oncology.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- The Rethinking Clinical Trials (REaCT) Program: A Pragmatic Research Strategy to Improve Cancer Care for Patients, Caregivers, and Healthcare Systems.Current oncology (Toronto, Ont.) · 2025Review
- Moving the needle on immune checkpoint inhibitors with novel targets: are we being TIMid or LAGging behind?The oncologist · 2025Article
- A real-world study on the efficacy and safety of low-dose PD-1 monoclonal antibody alone or in combination as the first-line treatment for advanced non-small cell lung cancer.Journal for immunotherapy of cancer · 2025Article
- Life-threatening toxicities upon Pembrolizumab intake: could pharmacokinetics be the bad guy?Cancer chemotherapy and pharmacology · 2024Article
- Phase 1 first-in-human dose-escalation study of ANV419 in patients with relapsed/refractory advanced solid tumors.Journal for immunotherapy of cancer · 2024Article
- Extending the dosing intervals of nivolumab: model-based simulations in unselected cancer patients.British journal of cancer · 2024Article
- Interventional pharmacoeconomics for immune checkpoint inhibitors through alternative dosing strategies.British journal of cancer · 2023Review
- Therapeutic drug monitoring of immune checkpoint inhibitors: based on their pharmacokinetic properties and biomarkers.Cancer chemotherapy and pharmacology · 2023Review
- In Silico Re-Optimization of Atezolizumab Dosing Using Population Pharmacokinetic Simulation and Exposure-Response Simulation.Journal of clinical pharmacology · 2023Article
- Cost Savings and Increased Access With Ultra-Low-Dose Immunotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Case report: Pharmacokinetics of pembrolizumab in a patient with stage IV non-small cell lung cancer after a single 200 mg administration.Frontiers in oncology · 2022Article
- Dosing Regimens of Immune Checkpoint Inhibitors: Attempts at Lower Dose, Less Frequency, Shorter Course.Frontiers in oncology · 2022Review
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.
Funding
Abstract
Nivolumab and pembrolizumab, anti-programmed cell death protein 1 monoclonal antibodies, have revolutionized oncology but are expensive. Using an interventional pharmacoeconomic approach, these drugs can be administered less often to reduce costs and increase patient convenience while maintaining efficacy. Both drugs are good candidates for less frequent dosing because of long half-lives and no evidence of a relationship of dose to efficacy. Established population pharmacokinetic models for both nivolumab and pembrolizumab were used to simulate profiles for multiple dosing regimens on 1000 randomly generated virtual patients. Simulations were initially performed on standard dose regimens to validate these in silico predictions. Next, simulations of nivolumab 0.3 mg/kg every 3 weeks revealed that >95% of patients maintained ≥1.5 μg/mL at steady state, which was inferred as the minimum effective concentration (MEC) for both drugs. Various alternative dosing regimens were simulated for both drugs to determine which regimen(s) can maintain this MEC in >95% of patients. Extended dosing regimens of nivolumab 240 mg every 4 weeks and 480 mg every 8 weeks along with pembrolizumab 200 mg every 6 weeks were simulated, showing that >95% of patients maintained MEC or greater. These simulations demonstrate the potential to reduce drug exposure by at least 50%, thus substantially reducing patient visits (as well as costs), while maintaining equivalent efficacy. These models provide the scientific justification for an ongoing prospective randomized clinical trial comparing standard interval fixed dosing with extended interval fixed dosing, and ultimately an efficacy-driven comparative trial.
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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.