Final results of the real-life observational VICTOR-6 study on metronomic chemotherapy in elderly metastatic breast cancer (MBC) patients.

Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT's activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75-98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3-4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

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

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.

Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3-10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8-11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3-15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Metronomic Chemotherapy in Triple-Negative Metastatic Breast Cancer: The Future Is Now?

Triple-negative breast cancer (TNBC) shows a very bad prognosis, even in early stages of disease. Metronomic chemotherapy refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen with no prolonged drug-free breaks that leads to antitumor activity. In the present article, we review preclinical and clinical data of metronomic administration of chemotherapy agents with or without biological agents in TNBC cell lines and patients, contextually reporting data from the VICTOR-2 study in the subgroup of patients with TNBC, in order to stimulate new ideas for the design of clinical trials in this subset of patients.

Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study.

PURPOSE: The VICTOR-1 study demonstrated that the all-oral metronomic combination of vinorelbine and capecitabine is highly active and well tolerated in hormone receptor-positive/HER2-negative patients. The VICTOR-2 study was designed to confirm these results. METHODS: Patients received mVNR 40 mg three times a week and mCAPE 500 mg three times a day, continuously. The primary endpoint was the clinical benefit rate (CBR); secondary endpoints were toxicity, objective response rate (ORR), and progression-free survival (PFS). RESULTS: Eighty patients were evaluable for the primary efficacy analysis. Median age was 65.3 years; most patients had HR-positive tumors (65 %). The CBR was 45.7 % (95 % CI 28.8-63.4) and 51.1 % (95 % CI 35.8-66.3) in first- and ≥ second-line therapy, respectively. The ORR was 35.5 % in first-line (95 % CI 19.2-54.6) and 25.6 % in ≥second-line (95 % CI 13.5-41.2). The median duration of response was 11.3 and 6.4 months and PFS rates at 1 year were 24.3 and 22.2 %, respectively. In triple-negative breast cancer patients (N = 28, 35 %) a lower, but clinically relevant CBR (35.7, 95 % CI 18.6-55.9) was observed. The main toxicities per cycle were non-febrile neutropenia (1.1 %), hand-foot syndrome (1.0 %), nausea and vomiting (1.0 %), leucopenia (0.8 %), fatigue (0.7 %), and diarrhea (0.4 %). CONCLUSION: The VICTOR-2 study confirms the clinical activity of mVNR and mCAPE in HER2-negative breast cancer patients, suggesting that the easy schedule of administration, which requires monthly blood tests and limits patients' dependence on hospitals, and the low cost of the drugs are valuable elements, even for countries with limited access to innovative or expensive drugs.