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.

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.

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure DR honoraria from Takeda. AS honoraria for editorial projects from Novartis Pharma; honoraria for travel grants from Pfizer and PharmaMar. AZ speakers’ bureau from Amgen, Merck Serono, Servier, Bayer, Pierre-Fabre. SL honoraria from Roche, Lilly, Bristol-Myers Squibb, Servier, and Merck Serono; research funding from Amgen and Merck Serono; consulting or advisory role with Amgen, Merck Serono, Lilly, and Servier. FP honoraria from Amgen, Merck Serono, Roche, Sanofi, Bayer, Servier, and Lilly; research funding from Bristol-Myers Squibb; consulting or advisory role with Amgen, Merck Serono, Bayer, Lilly, Sanofi, Roche, and Servier. AF honoraria from Roche, Amgen, Merck Serono, Celgene, Bayer, and Sanofi; research funding from Roche, Amgen, and Merck Serono paid to their institution. AA Science advisory board for Kyowa Hakko Kyrin, Pfizer, Angelini; honoraria from Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Otsuka, Novartis. CC honoraria from Roche, Amgen, Bayer, and Servier; research funding from Merck Serono; consulting or advisory role with Roche, Bayer, Amgen. All the other authors declared no competing interests.