KEY TAKEAWAYS
- The phase 2 METEORA-II randomized trial aimed to evaluate the efficacy of Oral VEX vs. IV Paclitaxel in ER+/ERBB2- MBC patients.
- 140 women aged 18 or older with ER+/ERBB2- MBC were randomized 1:1 at 15 Italian centers.
- The study measured time to treatment failure (TTF) as the primary endpoint and explored secondary endpoints like PFS, OS, and disease control rate.
- Oral VEX showed longer TTF and PFS than IV paclitaxel with manageable toxic effects. VEX may benefit ER+/ERBB2- MBC.
The researchers have been looking for effective treatments against estrogen receptor (ER)-positive, erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2/neu])-negative (ER+/ERBB2-) metastatic breast cancer (MBC). While endocrine therapy plus CDK 4/6 inhibitors were found to be effective as a first-line treatment, in the longer run, most patients developed resistance and were put in for chemo. The METEORA-II trial compared a metronomic all-oral regimen and intravenous (IV) chemotherapy to explore alternative options.
Conducted between September 2017 and January 2021 at 15 centers in Italy, this phase 2 randomized clinical trial involved 140 women aged 18 years and older with ER+/ERBB2- MBC. All participants were candidates for chemotherapy; some had previously received chemotherapy for MBC and/or endocrine therapy, including CDK4/6 inhibitors. The patients were divided into two groups: one received metronomic oral vinorelbine plus cyclophosphamide plus capecitabine (VEX), and the other received weekly IV paclitaxel. Investigator-assessed time to treatment failure (TTF) was considered as the primary endpoint. Progression-free survival (PFS), overall survival (OS), and disease control rate were considered as the secondary endpoints.
Out of 133 patients, 70 received VEX, and 63 received paclitaxel. The median age was 61 (range: 30-80). Investigators found that the VEX treatment prolonged TTF vs paclitaxel (hazard ratio [HR]: 0.61; 95% CI: 0.42-0.88; P = 0.008). Median TTF for VEX was 8.3 months (95% CI: 5.6-11.1), whereas, for paclitaxel, it was 5.7 months (95% CI: 4.1-6.1). TTF was 34.3% for VEX and 8.6% for paclitaxel at the 12-month. VEX exhibited favorable results for PFS compared to paclitaxel. PFS of 11.1 months (95% CI: 8.3-13.8) vs 6.9 months (95% CI: 5.4-10.1) for paclitaxel (HR: 0.67; 95% CI: 0.46-0.96, P = 0.03). The PFS rate for VEX was 43.5%, and for paclitaxel, it was 21.9% at 12 months. No notable difference was found in OS between the two treatments. A total of 55.6% of patients experienced disease progression, and 23% faced AEs. Patients in the VEX group had a higher incidence of at least one grade 3 or 4 targeted adverse events (42.9%; 95% CI: 31.1%-55.3%) compared to the paclitaxel group (28.6%; 95% CI: 17.9%-41.3%). Alopecia was essentially absent in the VEX group.
The trial demonstrated that oral VEX offers prolonged disease control for ER+/ERBB2- MBC, outperforming weekly paclitaxel in terms of TTF and PFS. While OS did not show improvement, the manageable toxic effects of the VEX regimen make it a promising alternative option.
Source: https://pubmed.ncbi.nlm.nih.gov/37440239/
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02954055
Munzone E, Regan MM, Cinieri S, Montagna E, Orlando L, Shi R, Campadelli E, Gianni L, Palleschi M, Petrelli F, Bengala C, Generali D, Collovà E, Puglisi F, Cretella E, Zamagni C, Chini C, Ruepp B, Loi S, Colleoni M; International Breast Cancer Study Group (IBCSG). Efficacy of Metronomic Oral Vinorelbine, Cyclophosphamide, and Capecitabine vs Weekly Intravenous Paclitaxel in Patients With Estrogen Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: Final Results From the Phase 2 METEORA-II Randomized Clinical Trial. JAMA Oncol. 2023 Jul 13:e232150. doi: 10.1001/jamaoncol.2023.2150. Epub ahead of print. PMID: 37440239; PMCID: PMC10346502.
