Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer

@article{Li2021TrilaciclibDS,
  title={Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer},
  author={Chao Li and Lowell L. Hart and Taofeek Kunle Owonikoko and Raid Aljumaily and Caio Max S Rocha Lima and Paul R. Conkling and Roy Timothy Webb and Robert M. Jotte and Steven Robert Schuster and William Jeffery Edenfield and Deborah A. Smith and Mark Sale and Patrick J. Roberts and Rajesh K. Malik and Jessica A. Sorrentino},
  journal={Cancer Chemotherapy and Pharmacology},
  year={2021},
  volume={87},
  pages={689 - 700}
}
Trilaciclib is a first-in-class CDK4/6 inhibitor that transiently arrests hematopoietic stem and progenitor cells (HSPCs) in the G1 phase of the cell cycle to preserve them from chemotherapy-induced damage (myelopreservation). We report integrated analyses of preclinical and clinical data that informed selection of the recommended Phase II dose (RP2D) used in trilaciclib trials in extensive-stage small cell lung cancer (ES-SCLC). A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model… 
Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer
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The drug–drug interaction and safety profiles of trilaciclib in these studies support its continued use in patients with extensive-stage small-cell lung cancer.
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