Metronomic chemotherapy (mCHT) in metastatic triple-negative breast cancer (TNBC) patients: results of the VICTOR-6 study

M Cazzaniga ,I Vallini,D Toniolo,A Fontana,A Grassadonia,M Nicolini,C Taverniti,V Leonardi,Alfredo Butera ,Rossana Berardi ,Filippo Giovanardi ,Daniele Santini ,P Spadaro,Mariangela Ciccarese ,M G Schintu,Anna Maria Baldelli ,Katia Cagossi ,Patrizia Vici ,Silvana Saracchini ,Antonio Febbraro ,Pierluigi Di Mauro ,Maria Giuseppa Sarobba ,Daniele Generali ,Giovanni Scognamiglio ,Viola Cogliati ,Vittorio Gebbia ,Carlo Putzu ,Paolo Marchetti ,Samanta Sarti ,Serena Capici ,Anna Turletti ,Enrico De Conciliis ,Francesco Ferraú ,Antonino Musolino ,Paolo Tralongo ,Ferdinando Riccardi ,Anna Gambaro ,Luigi Cavanna ,Elisabetta Cretella ,A Ferzi,Luca Clivio ,Saverio Cinieri ,Maria Rosaria Valerio ,Domenico Amoroso ,Ornella Garrone ,Luca Gianni ,Emilia Montagna ,Roberto Valenza ,Valter Torri

doi:10.1007/s10549-021-06375-5

Abstract

PurposeTriple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers and is associated with younger age at diagnosis, greater recurrence risk and shorter survival time. Therapeutic options are very scarce. Aim of the present analysis is to provide further insights into the clinical activity of metronomic chemotherapy (mCHT), in a real-life setting.MethodsWe used data included in the VICTOR-6 study for the present analysis. VICTOR-6 is an Italian multicentre retrospective cohort study, which collected data of metastatic breast cancer (MBC) patients who have received mCHT between 2011 and 2016. Amongst the 584 patients included in the study, 97 were triple negative. In 40.2% of the TNBC patients, mCHT was the first chemotherapy treatment, whereas 32.9% had received 2 or more lines of treatment for the metastatic disease. 45.4% out of 97 TNBC patients received a vinorelbine (VRL)-based regimen, which resulted in the most used type of mCHT, followed by cyclophosphamide (CTX)-based regimens (30.9%) and capecitabine (CAPE)-based combinations (22.7%).ResultsOverall response rate (ORR) and disease control rate (DCR) were 17.5% and 64.9%, respectively. Median progression free survival (PFS) and overall survival (OS) were 6.0 months (95% CI: 4.9–7.2) and 12.1 months (95% CI: 9.6–16.7). Median PFS was 6.9 months for CAPE-based regimens (95% CI: 5.0–18.4), 6.1 months (95% CI: 4.0–8.9) for CTX-based and 5.3 months (95% CI: 4.1–9.5) for VRL-based ones. Median OS was 18.2 months (95% CI: 9.1-NE) for CAPE-based regimens and 11.8 months for VRL- (95% CI: 9.3–16.7 and CTX-based ones (95%CI: 8.7–52.8). Tumour response, PFS and OS decreased proportionally in later lines.ConclusionThis analysis represents the largest series of TNBC patients treated with mCHT in a real-life setting and provides further insights into the advantages of using this strategy even in this poor prognosis subpopulation.

Highlights

Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers
The analysis presented in this paper explores the role of metronomic chemotherapy (mCHT) in advanced TNBC in a real-life setting as part of the VICTOR-6 study, an observational, retrospective study regarding the use of mCHT in the strategy of treatment of advanced breast cancer patients [12]
Other Authors [21] reported retrospective results of mCHT with different regimens in metastatic breast cancer patients; most of them showed that Overall Response Rate (ORR) were lower in TNBC subgroups in comparison to those observed in Luminal patients

Summary

Introduction

Triple-negative breast cancer (TNBC) represents a subtype of breast cancer which lacks the expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2): TNBC accounts for approximately 20% of newly diagnosed breast cancers. Due to its molecular features, the main therapeutic options do not include endocrine or targeted therapy, but are limited to conventional chemotherapy [2], antibody–drug conjugates [3] and immunotherapy [4] In this context, metronomic chemotherapy (mCHT) may represent a promising therapeutic strategy in the metastatic setting: it refers to the repeated administration of low doses of a chemotherapy agent to maintain prolonged and active plasma concentrations and to provide a favourable toxicity profile [5]. Demographic data, patients’ baseline characteristics and disease, plus treatment information were summarized with standard summary statistics (mean standard deviation and range for continuous data, relative and absolute frequencies for categorical data) Relationships of these variables with response were analysed by mead of a Mantel–Haenzel.

Study design

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Discussion

Conclusion