Efficacy of Metronomic Oral Vinorelbine, Cyclophosphamide, and Capecitabine vs Weekly Intravenous Paclitaxel in Patients With Estrogen Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer

Abstract

ImportanceIn spite of the effectiveness of endocrine therapy plus cyclin-dependent kinase (CDK) 4/6 inhibitors as the first-line treatment for estrogen receptor (ER)-positive, erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2/neu])-negative (ER+/ERBB2−) metastatic breast cancer (MBC), patients eventually develop resistance, and eventually most will receive chemotherapy. The METEORA-II trial compared a metronomic all-oral treatment with intravenous (IV) chemotherapy.ObjectiveTo compare the efficacy of the oral vinorelbine plus cyclophosphamide plus capecitabine (VEX) regimen vs weekly IV paclitaxel among patients with ER+/ERBB2− MBC who are candidates for chemotherapy.Design, Setting, and ParticipantsThis phase 2 randomized clinical trial including 140 women 18 years and older (randomized 1:1) with ER+/ERBB2− MBC was carried out from September 13, 2017, to January 14, 2021 at 15 centers in Italy. Eligible patients could have received 1 prior line of chemotherapy for MBC and/or 2 lines of endocrine therapy (including CDK4/6 inhibitors).InterventionsIn 4-week cycles, patients received either metronomic oral VEX or weekly IV paclitaxel.Main Outcomes and MeasuresThe primary end point was investigator-assessed time to treatment failure (TTF) defined as the interval between the date of randomization to the end of treatment (because of disease progression or lack of tolerability or because further trial treatment was declined). Secondary end points included progression-free survival (PFS), overall survival (OS), and disease control rate (complete or partial response or stable disease lasting for at least 24 weeks).ResultsIn total, 133 patients received either VEX (n = 70) or paclitaxel (n = 63) in 4-weekly cycles. The median age was 61 (range, 30-80) years. The VEX treatment significantly prolonged TTF vs paclitaxel (hazard ratio [HR], 0.61; 95% CI, 0.42-0.88; P = .008), median TTF was 8.3 (95% CI, 5.6-11.1) months for VEX vs 5.7 (95% CI, 4.1-6.1) months for paclitaxel, and the 12-month TTF was 34.3% for VEX vs 8.6% for paclitaxel. The median PFS was 11.1 (95% CI, 8.3-13.8) months vs 6.9 (95% CI, 5.4-10.1) months favoring VEX (HR, 0.67; 95% CI, 0.46-0.96, P = .03). The 12-month PFS was 43.5% for VEX vs 21.9% for paclitaxel. No difference in OS was found. The TF event for 55.6% of patients was progression of disease; for 23% it was AEs. More patients assigned to VEX had at least 1 grade 3 or 4 targeted adverse event (VEX, 42.9%; 95% CI, 31.1%-55.3% vs paclitaxel, 28.6%; 95% CI, 17.9%-41.3%), but essentially no alopecia.Conclusion and RelevanceThis randomized clinical trial found significantly prolonged TTF and PFS for oral VEX but no improvement in OS compared with intravenous paclitaxel, despite increased but still manageable toxic effects. The VEX regimen may provide more prolonged disease control than weekly paclitaxel for ER+/ERBB2− MBC.Trial RegistrationClinicalTrials.gov Identifier: NCT02954055

Cost-effectiveness of Metronomic chemotherapy vs Weekly Intravenous Paclitaxel in patients with ER+/HER2-Metastatic Breast Cancer

“…The METEORA-II trial showed that compared with weekly intravenous paclitaxel chemotherapy, oral vinorelbine + cyclophosphamide + capecitabine metronomic chemotherapy signi cantly prolonged TTF and PFS, and had a higher disease control rate (Munzone et al 2023). The OS of the two groups was similar.…”

“…Due to data availability and model assumptions, our economic model has some limitations. Firstly, the clinical data comes from the METEORA-II trial (Munzone et al 2023), where the majority of patients were from Italy and the proportion of Asians was small and unavailable, which may have a slight impact on our results. Due to the lack of research results on the health effects of breast cancer in different states in China, this limitation cannot be avoided at present.…”

“…The transition probability is the probability that an event will occur in a speci c period of time, and the transition probability in Markov's model is the probability of being in a different state of health during the cycle. In this study, the DEALE method was used to calculate the transition probability by using the data of the phase II clinical trial (Munzone et al 2023), and the transition probability calculation process is shown in Table 1. In addition, we converted all hazard ratios and survival rates into transition probabilities for one-year time periods.…”

“…The metronomic combination of capecitabine, vinorelbine, and cyclophosphamide (VEX regimen) was recently investigated in a phase II trial of patients with endocrine-responsive MBC. METEORA-II trial is a multicenter, open label, randomized controlled phase II clinical trial to evaluate the e cacy and safety of vinorelbine + Cyclophosphamide + Capecitabine (VEX regimen) in ER+/HER2 metastatic breast cancer patients (Munzone et al 2023). This study included a total of 140 patients who were randomly divided into the VEX group and the P group.…”

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

“…The majority used all oral metronomic therapy and different intravenous schedule as comparator. The results of a phase III study (METEORA) were presented recently, demonstrating the superiority of metronomic chemotherapy VEC (vinorelbine, cyclophosphamide and capecitabine) over weekly paclitaxel in terms of PFS and time-to-treatment failure (TTF) endpoints [ 14 ]. The METEORA study has thus established the VEC regimen as a safe and active option of MCT for the first-line treatment of advanced BC.…”