Pooled safety analysis from phase III studies of trifluridine/tipiracil in patients with metastatic gastric or gastroesophageal junction cancer and metastatic colorectal cancer

ESMO Open

article

E. Van Cutsem¹  H. Hochster²  K. Shitara³  R. Mayer⁴  A. Ohtsu³  A. Falcone⁵  T. Yoshino³  T. Doi³  D.H. Ilson⁶  H.-T. Arkenau⁷  B. George⁸  K.A. Benhadji⁹  L. Makris^1,10  J. Tabernero^1,11 

[1] University Hospitals Gasthuisberg Leuven and KU Leuven;Rutgers Cancer Institute;National Cancer Center Hospital East;Dana-Farber Cancer Institute;Azienda Ospedaliero Universitaria Pisana;Memorial Sloan Kettering Cancer Center;Sarah Cannon Research Institute, Cancer Institute, University College London;Medical College of Wisconsin;Taiho Oncology, Inc., Princeton;Stathmi, Inc;Vall d’Hebron Hospital Campus and Vall d’Hebron Institute of Oncology

关键词: trifluridine/tipiracil;    safety;    metastatic gastric cancer;    metastatic colorectal cancer;    neutropenia;    renal impairment;   

DOI  :  10.1016/j.esmoop.2022.100633

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Trifluridine/tipiracil (FTD/TPI) showed clinical benefit, including improved survival and manageable safety in previously treated patients with metastatic colorectal (mCRC) or gastric/gastroesophageal junction (mGC/GEJC) cancer in the phase III RECOURSE and TAGS trials, respectively. A pooled analysis was conducted to further characterize FTD/TPI safety, including management of haematologic toxicities and use in patients with renal or hepatic impairment.Patients and methods Adults with ≥2 prior regimens for advanced mGC/GEJC or mCRC were randomized (2 : 1) to FTD/TPI [35 mg/m2 twice daily days 1-5 and 8-12 (28-day cycle); same dosage in both trials] or placebo plus best supportive care. Adverse events (AEs) were summarized in the safety population (patients who received ≥1 dose) and analysed by renal/hepatic function.Results TAGS and RECOURSE included 335 and 533 FTD/TPI-treated and 168 and 265 placebo-treated patients, respectively. Overall safety of FTD/TPI was similar in TAGS and RECOURSE. Haematologic (neutropenia, anaemia) and gastrointestinal (nausea, diarrhoea) AEs were most commonly observed. Laboratory-assessed grade 3-4 neutropenia occurred in 37% (TAGS)/38% (RECOURSE) of FTD/TPI-treated patients (median onset: 29 days/55 days), and 96% (TAGS)/97% (RECOURSE) of cases resolved regardless of renal/hepatic function. Supportive medications for neutropenia were received by 17% (TAGS) and 9% (RECOURSE); febrile neutropenia was reported in 2% and 4%, respectively. Overall grade ≥3 AEs were more frequent in patients with moderate renal impairment [81% (TAGS); 85% (RECOURSE)] versus normal renal function (74%; 67%); anaemia and neutropenia were more common in patients with renal impairment. FTD/TPI safety (including haematologic AEs) was consistent across patients with normal and mildly impaired hepatic function.Conclusions These results support FTD/TPI as a well-tolerated treatment in patients with mGC/GEJC or mCRC, with a consistent safety profile. Safety was largely similar in patients with normal or mildly impaired renal/hepatic function; however, patients with renal impairment should be monitored for haematologic toxicities.

【 授权许可】

CC BY|CC BY-NC-ND