Cancer Immunotherapy Dosing: A Pharmacokinetic/Pharmacodynamic Perspective
Félicien Le Louedec,
Fanny Leenhardt,
Clémence Marin,
Étienne Chatelut,
Alexandre Evrard,
Joseph Ciccolini
Affiliations
Félicien Le Louedec
Institut Claudius-Regaud, Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole, and Cancer Research Center of Toulouse (CRCT), Inserm U1037, University of Toulouse, 31100 Toulouse, France
Fanny Leenhardt
Institut de Cancérologie de Montpellier (ICM) and Institut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, University of Montpellier, 34090 Montpellier, France
Clémence Marin
Assistance Publique—Hôpitaux de Marseille (AP-HM) and Simulation Modeling Adaptive Response for Therapeutics in cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, Aix Marseille University, 13009 Marseille, France
Étienne Chatelut
Institut Claudius-Regaud, Institut Universitaire du Cancer de Toulouse (IUCT)-Oncopole, and Cancer Research Center of Toulouse (CRCT), Inserm U1037, University of Toulouse, 31100 Toulouse, France
Alexandre Evrard
Centre Hospitalier Universitaire de Nîmes Carémeau, Nîmes, France and IRCM U1194, University of Montpellier, 34090 Montpellier, France
Joseph Ciccolini
Assistance Publique—Hôpitaux de Marseille (AP-HM) and Simulation Modeling Adaptive Response for Therapeutics in cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, Aix Marseille University, 13009 Marseille, France
Immune check-point inhibitors are drugs that are markedly different from other anticancer drugs because of their indirect mechanisms of antitumoral action and their apparently random effect in terms of efficacy and toxicity. This marked pharmacodynamics variability in patients calls for reconsidering to what extent approved dosing used in clinical practice are optimal or whether they should require efforts for customization in outlier patients. To better understand whether or not dosing could be an actionable item in oncology, in this review, preclinical and clinical development of immune checkpoint inhibitors are described, particularly from the angle of dose finding studies. Other issues in connection with dosing issues are developed, such as the flat dosing alternative, the putative role therapeutic drug monitoring could play, the rise of combinatorial strategies, and pharmaco-economic aspects.
