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Is There Any Room for Pharmacometrics With Immuno-Oncology Drugs? Input from the EORTC-PAMM Course on Preclinical and Early-phase Clinical Pharmacology

Anne Rodallec 1 Raphaelle Fanciullino 1 Sébastien Benzekry 2 Joseph Ciccolini 1
1 SMARTc - Simulation and Modeling of Adaptive Response for Therapeutics in Cancer
CRCM - Centre de Recherche en Cancérologie de Marseille
2 MONC - Modélisation Mathématique pour l'Oncologie
IMB - Institut de Mathématiques de Bordeaux, Institut Bergonié [Bordeaux], Inria Bordeaux - Sud-Ouest
Abstract : As part of the Pharmacology & Molecular Mechanisms (PAMM) Group, European Organization for Research and Treatment on Cancer (EORTC) 2019 winter Meeting Educational sessions, special focus has been placed on strategies to be undertaken to reduce the attrition rate when developing immune-oncology drugs. Immune checkpoint inhibitors have been game-changing drugs in several settings over the past decade such as melanoma and lung cancer. However, during the last years a rising number of studies failing to further improve clinical outcome in patients with cancer was recorded. Extensive pharmacometrics such as pharmacokinetics/ pharmacodynamics modeling support should help to overcome the current glass ceiling that has apparently been reached with immuno-oncology drugs (IOD). In particular, it should help in the issue of setting up combinatorial regimen (i.e. combining immune checkpoint inhibitors with cytotoxics, anti-angiogenesis or targeted therapies) that can no longer be addressed when following standard trial-and-error approaches, but rather by using mathematical-derived algorithms as decision-making tools by investigators for rational design. In routine clinical setting, developing therapeutic drug monitoring of immune checkpoint inhibitors with adaptive dosing strategies has been a long-neglected strategy. Still, substantial improvements might be achieved using dedicated tools for precision medicine and personalized medicine in immunotherapy.
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https://hal.inria.fr/hal-02383831
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Submitted on : Monday, December 9, 2019 - 11:26:40 AM
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Anne Rodallec, Raphaelle Fanciullino, Sébastien Benzekry, Joseph Ciccolini. Is There Any Room for Pharmacometrics With Immuno-Oncology Drugs? Input from the EORTC-PAMM Course on Preclinical and Early-phase Clinical Pharmacology. Anticancer Research, International Institute of Anticancer Research, 2019, 39 (7), pp.3419-3422. ⟨10.21873/anticanres.13486⟩. ⟨hal-02383831⟩

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