Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study

ESMO Open

article

R. Bordonaro¹  A. Calvo²  A. Auriemma³  A. Hollebecque⁴  G. Rubovszky⁵  M.P. Saunders⁶  Z. Pápai⁷  G. Prager⁸  A. Stein⁹  T. André^1,10  G. Argilés^1,11  A. Cubillo^1,12  L. Dahan^1,13  J. Edeline^1,14  C. Leger^1,15  V. Cattan^1,15  R. Fougeray^1,15  N. Amellal^1,15  J. Tabernero^1,11 

[1] Azienda Ospedaliera ARNAS Garibaldi;Gregorio Marañon University General Hospital;Azienda Ospedaliera Universitaria Integrat, University of Verona;Drug Development Department, Gustave Roussy Cancer Campus;Department of Medical Oncology and Clinical Pharmacology, National Institute of Oncology Hungary;Christie NHS Foundation Trust;Department of Medical Oncology, Duna Medical Centre;Comprehensive Cancer Centre Vienna, Medical University Vienna;UKE Universitätsklinikum Hamburg-Eppendorf KMTZ;Sorbonne Université et Hôpital Saint-Antoine;Vall d"Hebron University Hospital and Institute of Oncology;Medical Oncology, Hospital Universitario Madrid Sanchinarro Centro Integral Oncologico Clara Campal;Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Centre d"Essais Précoces en Cancérologie de Marseille CLIP;Department of Medical Oncology, Centre Eugene Marquis;Institut de Recherches Internationales Servier;UVic-UCC

关键词: trifluridine/tipiracil;    oxaliplatin;    metastatic colorectal cancer;    fluoropyrimidines;   

DOI  :  10.1016/j.esmoop.2021.100270

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment.Patients and methods In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status.Results In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months.Conclusion FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.

【 授权许可】

CC BY|CC BY-NC-ND