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

被引:10
|
作者
Bordonaro, R. [1 ]
Calvo, A. [2 ]
Auriemma, A. [3 ]
Hollebecque, A. [4 ]
Rubovszky, G. [5 ]
Saunders, M. P. [6 ]
Papai, Z. [7 ]
Prager, G. [8 ]
Stein, A. [9 ]
Andre, T. [10 ,11 ]
Argiles, G. [12 ,13 ]
Cubillo, A. [14 ]
Dahan, L. [15 ,16 ]
Edeline, J. [17 ]
Leger, C.
Cattan, V. [18 ]
Fougeray, R. [18 ]
Amellal, N. [18 ]
Tabernero, J. [12 ,13 ,19 ]
机构
[1] Azienda Osped ARNAS Garibaldi, Via Palermo 636, Catania, Italy
[2] Gregorio Maranon Univ Gen Hosp, Madrid, Spain
[3] Univ Verona, Azienda Osped Univ Integrat, Verona, Italy
[4] Gustave Roussy Canc Campus, Drug Dev Dept, Villejuif, France
[5] Natl Inst Oncol Hungary, Dept Med Oncol & Clin Pharmacol, Budapest, Hungary
[6] Christie NHS Fdn Trust, Manchester, Lancs, England
[7] Duna Med Ctr, Dept Med Oncol, Budapest, Hungary
[8] Med Univ Vienna, Comprehens Canc Ctr Vienna, Vienna, Austria
[9] UKE Univ Klinikum Hamburg Eppendorf KMTZ, Hamburg, Germany
[10] Sorbonne Univ, Paris, France
[11] Hop St Antoine, Serv Oncol Med, Paris, France
[12] Vall dHebron Univ Hosp, Barcelona, Spain
[13] Inst Oncol VHIO, Barcelona, Spain
[14] Hosp Univ Madrid, Sanchinarro Ctr Integral Oncologico Clara Campal, Med Oncol, Madrid, Spain
[15] Aix Marseille Univ, Marseille, France
[16] AP HM, Ctr Essais Prec Cancerol Marseille CLIP, Marseille, France
[17] ARPEGO Network, Ctr Eugene Marquis, Dept Med Oncol, Rennes, France
[18] Inst Rech Int Servier, Suresnes, France
[19] UVic UCC, IOB Quiron, Barcelona, Spain
关键词
trifluridine/tipiracil; oxaliplatin; metastatic colorectal cancer; fluoropyrimidines; ORAL CHEMOTHERAPEUTIC-AGENT; TAS-102; CONTINUATION; PROGRESSION; MECHANISM; EFFICACY;
D O I
10.1016/j.esmoop.2021.100270
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
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/m(2) (twice daily, days 1-5) plus oxaliplatin 85 mg/m(2) (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.
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页数:7
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