Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Sep 1;9(9):1267-1272.
doi: 10.1001/jamaoncol.2023.2150.

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

Elisabetta Munzone  1 , Meredith M Regan  2 , Saverio Cinieri  3 , Emilia Montagna  1 , Laura Orlando  3 , Ruichao Shi  4 , Enrico Campadelli  5 , Lorenzo Gianni  6 , Michela Palleschi  7 , Fausto Petrelli  8 , Carmelo Bengala  9 , Daniele Generali  10 , Elena Collovà  11 , Fabio Puglisi  12   13 , Elisabetta Cretella  14 , Claudio Zamagni  15 , Claudio Chini  16 , Barbara Ruepp  17 , Sherene Loi  17   18 , Marco Colleoni  1   17 ; International Breast Cancer Study Group (IBCSG)
Collaborators, Affiliations
Clinical Trial

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

Elisabetta Munzone et al. JAMA Oncol. .

Abstract

Importance: In 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.

Objective: To 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 participants: This 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).

Interventions: In 4-week cycles, patients received either metronomic oral VEX or weekly IV paclitaxel.

Main outcomes and measures: The 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).

Results: In 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 relevance: This 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 registration: ClinicalTrials.gov Identifier: NCT02954055.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Munzone reported receiving grants from the Fondazione Umberto Veronesi during the conduct of the study and consulting or advisory fees from Eisai, Exact Sciences, MSD Oncology, Daiichi-Sankyo/AstraZeneca, Pfizer, and Seagen outside the submitted work. Dr Regan reported receiving funding from Pierre Fabre and research funding for her institution from the International Breast Cancer Study Group (IBCSG) Statistical Center during the conduct of the study and research funding from Novartis, Pfizer, Ipsen, TerSera, Roche, Bayer, and Bristol Myers Squibb; nonfinancial support from AstraZeneca (drug supply); consulting fees from Ipsen, and DebioPharm; and personal fees from Bristol Myers Squibb, Tolmar, AstraZeneca, and TerSera outside the submitted work. Dr Cinieri reported holding the position of AIOM (Associazione Italiana Oncologi Medici) National Presidente. Dr Montagna reported receiving grants from the Fondazione Umberto Veronesi during the conduct of the study and speaker honoraria from Novartis and AstraZeneca outside the submitted work. Dr Gianni reported receiving personal fees from the advisory boards of AstraZeneca and Seagen; and fees for travel, accommodations, and expenses from Novartis, Pfizer, Roche, and Daiichi-Sankyo/AstraZeneca outside the submitted work. Dr Puglisi reported receiving personal fees from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Lilly, Exact Sciences, Gilead Sciences, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris and grants from AstraZeneca, Eisai, and Roche outside the submitted work. Dr Zamagni reported receiving IBCSG research funding for his institution during the conduct of the study; consulting or advisory fees from Roche, Eisai, Novartis, AstraZeneca, Pfizer, PharmaMar, Celgene, Lilly, Amgen, Daiichi-Sankyo, Exact Sciences, MSD, and GSK; research funding for his institution from Roche/Genentech, AstraZeneca, Novartis, Medivation, AbbVie, Pfizer, Array BioPharma, Morphotek, Synthon, Seattle Genetics, Gilead Sciences, and Daiichi-Sankyo; consulting or advisory fees from Seattle Genetics and Gilead; and fees for travel and accommodations from Roche, Novartis, Pfizer, AstraZeneca, Daiichi-Sankyo, and Gilead outside the submitted work. Dr Loi reported receiving research funding for her institution from Novartis, Bristol Myers Squibb, Merck, Puma Biotechnology, Lilly, Nektar Therapeutics, AstraZeneca, and Seattle Genetics; consulting fees from Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Lilly, Pfizer, Gilead Therapeutics, and Roche-Genentech; and fees for the institution from Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Daiichi-Sankyo, Merck, Amunix, Tallac Therapeutics, Lilly, and Bristol Myers Squibb outside the submitted work. Dr Colleoni reported receiving IBCSG financial support and grants from Fondazione Umberto Veronesi during the conduct of the study and grants from Roche outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. METEORA-II Trial CONSORT Flow Diagram
IV indicates intravenous; VEX, vinorelbine plus cyclophosphamide plus capecitabine.
Figure 2.
Figure 2.. Time-to-treatment Failure (TTF) in the METEORA-II Trial
The end-of-treatment date for defining TTF was the date the last paclitaxel intravenous dose was administered plus 7 days or the date when at least 1 of the 3 oral medications (vinorelbine plus cyclophosphamide plus capecitabine) was taken for the last time. A maximum 3-week delay of administration of any study medication was allowed. VEX indicates vinorelbine plus cyclophosphamide plus capecitabine.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660 - DOI - PubMed
    1. Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E. Locally recurrent or metastatic breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 (suppl 7). - PubMed
    1. Munzone E, Pagan E, Bagnardi V, et al. . Systematic review and meta-analysis of post-progression outcomes in ER+/HER2- metastatic breast cancer after CDK4/6 inhibitors within randomized clinical trials. ESMO Open. 2021;6(6):100332. doi:10.1016/j.esmoop.2021.100332 - DOI - PMC - PubMed
    1. Montagna E, Palazzo A, Maisonneuve P, et al. . Safety and efficacy study of metronomic vinorelbine, cyclophosphamide plus capecitabine in metastatic breast cancer: a phase II trial. Cancer Lett. 2017;400:276-281. doi:10.1016/j.canlet.2017.01.027 - DOI - PubMed
    1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi:10.1016/j.ejca.2008.10.026 - DOI - PubMed

Publication types

Associated data