PMID- 33743073 OWN - NLM STAT- MEDLINE DCOM- 20211021 LR - 20211021 IS - 1432-1335 (Electronic) IS - 0171-5216 (Print) IS - 0171-5216 (Linking) VI - 147 IP - 11 DP - 2021 Nov TI - Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2- breast cancer resistant to endocrine therapy: VinoMetro-AGO-B-046. PG - 3391-3400 LID - 10.1007/s00432-021-03599-2 [doi] AB - PURPOSE: Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. METHODS: VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2- MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. RESULTS: Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1-55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3-12.7). Grade 3-4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. CONCLUSION: VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2- MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016. CI - (c) 2021. The Author(s). FAU - Krajnak, Slavomir AU - Krajnak S AD - Department of Gynaecology and Obstetrics, University Medical Centre, Mainz, Germany. FAU - Decker, Thomas AU - Decker T AD - Haematology and Oncology Outpatient Clinic, Ravensburg, Germany. FAU - Schollenberger, Lukas AU - Schollenberger L AD - Interdisciplinary Centre for Clinical Trials, University Medical Centre, Mainz, Germany. FAU - Rose, Christian AU - Rose C AD - Pierre-Fabre GmbH, Freiburg, Germany. FAU - Ruckes, Christian AU - Ruckes C AD - Interdisciplinary Centre for Clinical Trials, University Medical Centre, Mainz, Germany. FAU - Fehm, Tanja AU - Fehm T AD - Department of Gynaecology and Obstetrics, University Medical Centre, Dusseldorf, Germany. FAU - Thomssen, Christoph AU - Thomssen C AD - Department of Gynaecology, University Medical Centre, Halle (Saale), Germany. FAU - Harbeck, Nadia AU - Harbeck N AD - Breast Centre, Department of Gynaecology and Obstetrics and CCC Munich LMU, University Hospital, LMU Munich, Munich, Germany. FAU - Schmidt, Marcus AU - Schmidt M AUID- ORCID: 0000-0003-1365-2414 AD - Department of Gynaecology and Obstetrics, University Medical Centre, Mainz, Germany. marcus.schmidt@unimedizin-mainz.de. LA - eng SI - ClinicalTrials.gov/NCT03007992 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20210320 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Steroid) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - Q6C979R91Y (Vinorelbine) SB - IM MH - Administration, Metronomic MH - Administration, Oral MH - Aged MH - Antineoplastic Agents, Phytogenic/administration & dosage MH - Breast Neoplasms/*drug therapy/metabolism/pathology MH - Drug Resistance, Neoplasm MH - Female MH - Humans MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Progression-Free Survival MH - Receptor, ErbB-2/metabolism MH - Receptors, Estrogen MH - Receptors, Steroid/metabolism MH - Vinorelbine/*administration & dosage PMC - PMC8484172 OTO - NOTNLM OT - Clinical benefit rate OT - Daily oral vinorelbine OT - Metastatic breast cancer OT - Metronomic chemotherapy COIS- Slavomir Krajnak received speaker honoraria from Roche Pharma AG, research funding from Novartis and travel reimbursement from PharmaMar outside the submitted work. Thomas Decker reports personal fees from Lilly and Novartis outside the submitted work. Christian Rose is an employee of Pierre-Fabre. Tanja Fehm received honoraria from Onkowissen, Pfizer, Novartis, Roche, MSD, Daichii Sankyo, AstraZeneca outside the submitted work. Christoph Thomssen received honoraria for advisory boards and lectures from Amgen, Astra-Zeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Vifor outside the submitted work; he received research support (by discount prizes) from American Diagnostica, Affymetrix, Nanostring. Nadia Harbeck received honoraria for consulting and/or lectures from Astra Zeneca, Daiichi-Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz/Hexal, Seattle Genetics outside the submitted work. Marcus Schmidt reports grants from Pierre-Fable during the conduct of the study; he received honoraria for consulting and/or lectures from Amgen, AstraZeneca, Eisai, Lilly, Myelo Therapeutics, Novartis, Pantarhei Bioscience, Pfizer, Pierre-Fabre, Roche and Seattle Genetics outside the submitted work. He received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Myelo Therapeutics, Novartis, Palleos, Pantarhei Bioscience, Pierre-Fabre, and Roche. He received travel reimbursement from BioNTech, Pantarhei Bioscience, Pfizer and Roche; in addition, he has a patent for EP 2951317 B1 and a patent for EP 2390370 B1 issued. All other authors declare that they have no conflict of interest. EDAT- 2021/03/21 06:00 MHDA- 2023/02/25 06:00 PMCR- 2021/03/20 CRDT- 2021/03/20 17:09 PHST- 2021/02/23 00:00 [received] PHST- 2021/03/12 00:00 [accepted] PHST- 2021/03/21 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2021/03/20 17:09 [entrez] PHST- 2021/03/20 00:00 [pmc-release] AID - 10.1007/s00432-021-03599-2 [pii] AID - 3599 [pii] AID - 10.1007/s00432-021-03599-2 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2021 Nov;147(11):3391-3400. doi: 10.1007/s00432-021-03599-2. Epub 2021 Mar 20.