Dataset Information

Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study.

ABSTRACT: BACKGROUND:Anticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor ? (TGF-?) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin. METHODS:TGF-?, tumour necrosis factor ?, vascular endothelial growth factor, IL-6, IL-8, IL-10, IL-21 and C-C motif chemokine ligand-2 levels were assessed in peripheral blood samples obtained from seven healthy volunteers and 41 patients at baseline (T0), after four cycles of eribulin (T1) and at disease progression (TPD). Baseline values and longitudinal changes in cytokine levels were then related to clinical outcome. RESULTS:In the 41 patients, high IL-6 and IL-8 (above the median) at T0 significantly correlated with worse survival. At T1, IL-21 significantly decreased in patients with TPD within the fourth course of treatment, compared with patients without progression. TGF-? and IL-8 above the median and IL-21 below the median at T1 significantly correlates with worse progression free survival (PFS). Patients exhibiting an increase of TGF-? or a decline of IL-21 between T0 and T1 showed a significantly worse PFS. Multivariate Cox regression analysis showed that only plasma TGF-? changes at T1 correlated with survival. At TPD, TGF-? significantly increased in all patients. CONCLUSIONS:We observed a significant correlation between TGF-? decline during eribulin treatment and outcome in patients with metastatic breast cancer. Altogether, our data suggest that eribulin treatment might interfere with the tumour microenvironment.

SUBMITTER: Garrone O

PROVIDER: S-EPMC7555105 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study.

Garrone Ornella O Michelotti Andrea A Paccagnella Matteo M Montemurro Filippo F Vandone Anna Maria AM Abbona Andrea A Geuna Elena E Vanella Paola P De Angelis Claudia C Lo Nigro Cristiana C Falletta Antonella A Crosetto Nicola N Di Maio Massimo M Merlano Marco M

ESMO open 20201001 5

<h4>Background</h4>Anticancer drugs can interact with the tumour microenvironment and their effects could be exploited to favour anticancer immune response. Eribulin contributes to tumour vasculature remodelling and transforming growth factor β (TGF-β) modulation in experimental models and in humans. We performed a prospective, translational, exploratory analysis of the levels of circulating cytokines at different time points in patients with metastatic breast cancer treated with eribulin.<h4>Me ...[more]

PMID: 33051191

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Project description: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. Highlights • FOLFOXIRI/bevacizumab is associated with a higher incidence of G3-4 neutropenia and FN than doublets/bevacizumab.• FN occurred in <10% of patients receiving FOLFOXIRI/bevacizumab and mostly as low-risk episodes.• Older patients and females show a significantly higher risk of G3-4 neutropenia.• Longitudinal analysis of neutropenia showed different patterns of evolution with doublets versus triplet.• Neither G3-4 neutropenia nor FN impaired treatment efficacy.

Dataset Information

Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study.

Publications

Exploratory analysis of circulating cytokines in patients with metastatic breast cancer treated with eribulin: the TRANSERI-GONO (Gruppo Oncologico del Nord Ovest) study.

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