Clinical impact of neutropenia and febrile neutropenia in metastatic colorectal cancer patients treated with FOLFOXIRI/bevacizumab: a pooled analysis of TRIBE and TRIBE2 studies by GONO

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D. Rossini¹  A. Boccaccino¹  A. Sbrana³  F. Daniel⁵  B. Borelli¹  A. Raimondi⁶  D. Santini⁷  V. Conca¹  G. Tomasello⁸  S. Caponnetto⁹  F. Marmorino¹  A. Zaniboni^1,10  A. Buonadonna^1,11  G. Masi¹  S. Lonardi^1,12  F. Pietrantonio⁶  A. Falcone¹  A. Antonuzzo²  C. Cremolini¹ 

[1] Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana;Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa;Service of Pneumo-Oncology, Unit of Pneumology, Azienda Ospedaliero-Universitaria Pisana;Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa;Oncology Unit 1, Department of Oncology IOV – IRCCS;Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori;Department of Medical Oncology, University Campus Bio-Medico;UOC Oncologia Medica, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico;Policlinico Umberto I, Oncologia B, Department of Radiological, Oncological and Pathological Sciences, La Sapienza University;Medical Oncology Unit, Poliambulanza Foundation;Department of Medical Oncology;Oncology Unit 3, Veneto Institute of Oncology IOV-IRCCS;Unit of Medical Oncology 1, Azienda Ospedaliero-Universitaria Pisana

关键词: metastatic colorectal cancer;    FOLFOXIRI;    neutropenia;    febrile neutropenia;    G-CSF;    longitudinal toxicity over time;   

DOI  :  10.1016/j.esmoop.2021.100293

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background TRIBE and TRIBE-2 studies demonstrated higher benefit from FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan)/bevacizumab compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX/bevacizumab as an upfront option for metastatic colorectal cancer patients, with more toxicities. We focused on the incidence and longitudinal dynamics of neutropenia and febrile neutropenia (FN) in the two studies, to evaluate their clinical relevance, the magnitude of impact of FOLFOXIRI/bevacizumab, and the role of risk factors in predicting their occurrence.Methods The overall incidence of grade 3-4 (G3-4) neutropenia and FN, the time to their onset, the use of granulocyte colony-stimulating factor, and the association with risk factors were evaluated in the overall population and according to treatment arm. FN episodes were assessed by Multinational Association for Supportive Care in Cancer (MASCC) score.Results Among 1155 patients, 568 (49%) received FOLFOXIRI/bevacizumab. Overall, 410 (35%) experienced G3-4 neutropenia and 70 (6%) FN, 21 (2%) at high risk. FOLFOXIRI/bevacizumab was associated with higher incidence of neutropenia (51% versus 21%, P < 0.001), FN (8% versus 4%, P = 0.02), and high-risk FN [18 (3%) versus 3 (1%), P = 0.015]. No related deaths were observed. The first episode of G3-4 neutropenia and FN occurred mainly in the first 2 months in both arms. Longitudinal analysis showed different patterns of evolution over cycles between the arms (P < 0.001) G3-4 neutropenia being more frequent in the first cycles with FOLFOXIRI/bevacizumab. Older patients (P = 0.01) and females (P < 0.001) had a significantly higher risk of G3-4 neutropenia. No significant interaction effect between arm and analysed risk factors in terms of risk of G3-4 neutropenia or FN was observed. The incidence of FN among older females receiving FOLFOXIRI/bevacizumab was 12%. Neither G3-4 neutropenia nor FN impaired efficacy in terms of overall response rate, progression-free survival, and overall survival.Conclusions FOLFOXIRI/bevacizumab has a higher risk of G3-4 neutropenia and FN than doublets/bevacizumab. FN occurred in <10% of patients, mostly as low-risk episodes. A closer monitoring during the first 2 months is recommended; prophylactic use of granulocyte colony-stimulating factor may be considered for older females.

【 授权许可】

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