ArticleCPT: pharmacometrics & systems pharmacology2023
Virtual clinical trials: A tool for predicting patients who may benefit from treatment beyond progression with pembrolizumab in non-small cell lung cancer.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Learning Patient Similarity from Genomics for Precision Oncology.medRxiv : the preprint server for health sciences · 2025Article
- A Step-by-Step Workflow for Performing In Silico Clinical Trials With Nonlinear Mixed Effects Models.CPT: pharmacometrics & systems pharmacology · 2025Article
- A scoping review of human digital twins in healthcare applications and usage patterns.NPJ digital medicine · 2025Article
- Digital Twins for Personalized Medicine Require Epidemiological Data and Mathematical Modeling: Viewpoint.Journal of medical Internet research · 2025Article
- Advances and critical aspects in cancer treatment development using digital twins.Briefings in bioinformatics · 2025Review
- Enhancing clinical outcome predictions through effective sample size evaluation in graph-based digital twin modeling.BioData mining · 2025Article
- From virtual to reality: innovative practices of digital twins in tumor therapy.Journal of translational medicine · 2025Review
- Digital Twins for Clinical and Operational Decision-Making: Scoping Review.Journal of medical Internet research · 2025Article
- Article
- Evolution of digital twins in precision health applications: a scoping review study.Research square · 2024Article
- Realizing the promise of Project Optimus: Challenges and emerging opportunities for dose optimization in oncology drug development.CPT: pharmacometrics & systems pharmacology · 2024Review
- Digital twins for health: a scoping review.NPJ digital medicine · 2024Article
- In silico trial for the assessment of givinostat dose adjustment rules based on the management of key hematological parameters in polycythemia vera patients.CPT: pharmacometrics & systems pharmacology · 2024Article
- Artificial intelligence across oncology specialties: current applications and emerging tools.BMJ oncology · 2024Review
- Virtual clinical trials: A tool for predicting patients who may benefit from treatment beyond progression with pembrolizumab in non-small cell lung cancer.CPT: pharmacometrics & systems pharmacology · 2023Article
- Incorporating lesion-to-lesion heterogeneity into early oncology decision making.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Enrolling patients in immunotherapy clinical trials is becoming increasingly competitive. Virtual clinical trials can help investigators answer key questions despite this. For example, pembrolizumab is the recommended first-line treatment for non-small cell lung cancer (NSCLC) with no driver alterations and a programmed death ligand 1 (PD-L1) Tumor Proportion Score ≥50%. Salvage therapies for relapsed/refractory patients are limited. Retrospective studies suggest that a subset of patients may benefit from pembrolizumab beyond progression; these results have not been validated in a prospective study. We constructed digital twins of patients and simulated clinical trials to predict the best salvage therapy after progressive disease (PD) on pembrolizumab. Response dynamics were evaluated at the lesion level to represent patients who experience systemic PD while individual lesions continue shrinking. With >25,000 radiographic lesion measurements from >500 patients, we simulated responses to pembrolizumab, chemotherapy, and PD on pembrolizumab followed by either pembrolizumab beyond progression or salvage chemotherapy. Switching all progressors to salvage chemotherapy was suboptimal. Virtual trials predicted progression-free survival (PFS) from pembrolizumab beyond progression to be comparable with salvage chemotherapy in patients whose PD was due to nontarget progression. A PFS-optimized regimen may improve disease control rates ≥15%. Pembrolizumab beyond progression may benefit a subset of patients with PD-L1-high, driver alteration-free NSCLC, but prospective studies are warranted.
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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.