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oai:recercat.cat:11351/64072025-10-24T10:40:16Zcom_2072_378070com_2072_378040col_2072_378092

Neutropenia and survival outcomes in metastatic colorectal cancer patients treated with trifluridine/tipiracil in the RECOURSE and J003 trials Yoshino, T. Cleary, J. M. Van Cutsem, Eric Mayer, Robert Ohtsu, Atsushi Shinozaki, E. Argilés Martinez, Guillem Institut Català de la Salut [Yoshino T, Ohtsu A] Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. [Cleary JM, Mayer RJ] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA. [Van Cutsem E] Division of Digestive Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. [Shinozaki E] Department of Gastroenterology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. [Argilés G] Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Recte - Càncer - Quimioteràpia Còlon - Càncer - Quimioteràpia Neutropènia DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Leukocyte Disorders::Leukopenia::Agranulocytosis::Neutropenia ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos leucocitarios::leucopenia::agranulocitosis::neutropenia Neutropènia induïda per quimioteràpia; Càncer colorectal metastàtic Neutropenia inducida por quimioterapia; Cáncer colorrectal metastásico Chemotherapy-induced neutropenia; Metastatic colorectal cancer Background The phase II J003 (N = 169) and phase III RECOURSE (N = 800) trials demonstrated a significant improvement in survival with trifluridine (FTD)/tipiracil (TPI) versus placebo in patients with refractory metastatic colorectal cancer. This post hoc analysis investigated pharmacokinetic data of FTD/TPI exposure and pharmacodynamic markers, such as chemotherapy-induced neutropenia (CIN) and clinical outcomes. Patients and methods A total of 210 patients from RECOURSE were enrolled in this substudy. A limited sampling approach was used, with three pharmacokinetic samples drawn on day 12 of cycle 1. Patients were categorized as being above or below the median area under the plasma concentration–time curve (AUC) for FTD and TPI. We conducted a post hoc analysis using the entire RECOURSE population to determine the correlations between CIN and clinical outcome. We then carried out a similar analysis on the J003 trial to validate the results. Results In the RECOURSE subset, patients in the high FTD AUC group had a significantly increased CIN risk. Analyses of the entire population demonstrated that FTD/TPI-treated patients with CIN of any grade in cycles 1 and 2 had significantly longer median overall survival (OS) and progression-free survival (PFS) than patients who did not develop CIN and patients in the placebo group. Patients who required an FTD/TPI treatment delay had increased OS and PFS versus those in the placebo group and those who did not develop CIN. Similar results were obtained in the J003 cohort. Conclusions In RECOURSE, patients with higher FTD drug exposure had an increased CIN risk. FTD/TPI-treated patients who developed CIN had improved OS and PFS versus those in the placebo group and those who did not develop CIN. Similar findings were reported in the J003 cohort, thus validating the RECOURSE results. The occurrence of CIN may be a useful predictor of treatment outcomes for FTD/TPI-treated patients. This study was supported by Taiho Pharmaceutical Co., Ltd., Tokyo, Japan and Taiho Oncology, Inc., Princeton, NJ, USA. No grant numbers are applicable. 2021-10-19T10:19:26Z 2021-10-19T10:19:26Z 2020-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Yoshino T, Cleary JM, Van Cutsem E, Mayer RJ, Ohtsu A, Shinozaki E, et al. Neutropenia and survival outcomes in metastatic colorectal cancer patients treated with trifluridine/tipiracil in the RECOURSE and J003 trials. Ann Oncol. 2020 Jan;31(1):88–95. 0923-7534 https://hdl.handle.net/11351/6407 10.1016/j.annonc.2019.10.005 31912801 000516712000014 http://hdl.handle.net/11351/6407 eng Annals of Oncology;31(1) https://doi.org/10.1016/j.annonc.2019.10.005 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf Elsevier Scientia