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

Abstract

Purpose 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 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. Methods We 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%). Results Overall 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. Conclusion This 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.

Personalised Therapies for Metastatic Triple-Negative Breast Cancer: When Target Is Not Everything

“…Moreover, longer PFS was observed when mCHT was used in the first-line setting than in the second and subsequent lines. Median OS was 18.2 months for capecitabine-based regimens and 11.8 months for vinorelbine- and CTX-based ones, while similar results were observed for OS according to the line of treatment [ 105 ].…”

Metronomic Chemotherapy is an Effective and Well Tolerated Treatment in Advanced Triple Negative Breast Cancer Patients: A Case Report of a Very Long Responder and Literature Review

“…This duration of response is extraordinary if we consider that, the median overall survival of mTNBC is around 18 months, as also emerged from the VICTOR-6 analysis of TNBC patients treated with metronomic CAPE-based regimens [14]. This can be partially explained by the change in tumour biology from initial diagnosis to disease recurrence as evidenced by the subgroup analysis of the phase II trial conducted by Montagna et al, in which the PFS rate at 1 year was significantly higher in patients with ER-positive versus ER-negative tumours at primary diagnosis [15]. Furthermore, the low disease burden and the absence of visceral localizations probably represented favourable prognostic factors being expression of a relatively indolent clinical course, a rare behaviour for mTNBC.…”

“…Montagna et al, in another phase II trial, tested the combination of triple drug oral chemotherapy consisting of vinorelbine, cyclophosphamide and capecitabine (VEX regimen) in 25 previously untreated patients: the overall response rate (ORR) was 27% and the CBR was 50%; median time to progression (TTP) and median time to death were 6.4 and 18.4 months respectively. The VEX regimen was relatively well tolerated with only 9% of grade 3 hand-foot-syndrome (HFS) [15]. At the second disease relapse, once again with an oligo metastatic spread (only later cervical lymph nodes) without visceral localizations, it was decided to continue metronomic chemotherapy adding capecitabine to vinorelbine.…”

Phase II randomized trial comparing metronomic anthracycline-containing chemotherapy versus standard schedule in untreated HER2 negative advanced breast cancer: activity and quality of life results of the GOIM 21003 trial

“…For these reasons, the introduction of chemotherapy in HR positive disease is increasingly delayed. Moreover, in our study very few patients received endocrine-therapy as first-line treatment for their ABC, in contrast with all the International guidelines available [ 16 ].…”