Thomas Decker1, Norbert Marschner2, Axel Muendlein3, Anja Welt4, Volker Hagen5, Jaqueline Rauh6, Helge Schröder7, Peter Jaehnig8, Karin Potthoff9, Christian Lerchenmüller10. 1. Onkologie Ravensburg, Elisabethenstraße 19, 88212, Ravensburg, Germany. decker@onkonet.eu. 2. Praxis für interdisziplinäre Onkologie & Hämatologie GbR, Wirthstraße 11c, 79110, Freiburg Im Breisgau, Germany. 3. VIVIT Labor, Campus V, Stadtstraße 33, 6850, Dornbirn, Austria. 4. Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum, Universitätsklinikum Essen, Hufelandstraße 55, 45147, Essen, Germany. 5. St Johannes Hospital, Johannesstraße 9-13, 44137, Dortmund, Germany. 6. Gemeinschaftspraxis für Innere Medizin, Pferdebachstraße 29, 58455, Witten, Germany. 7. AIO-Studien-gGmbH, Kuno-Fischer-Straße 8, 14057, Berlin, Germany. 8. ICRC-Weyer GmbH, Bölschestraße 35, 12587, Berlin, Germany. 9. iOMEDICO AG, Ellen-Gottlieb-Straße 19, 79106, Freiburg Im Breisgau, Germany. 10. Gemeinschaftspraxis für Hämatologie und Onkologie, Steinfurter Straße 60B, 48149, Münster, Germany.
Abstract
PURPOSE: Improving the outcome of patients with HER2-negative metastatic breast cancer experiencing tumour progression following first-line chemotherapy remains an urgent medical need. The purpose of the VicTORia trial was to show superiority of everolimus in combination with vinorelbine versus vinorelbine monotherapy as second-line chemotherapy for patients with advanced HER2 negative breast cancer. METHODS: In this randomised phase II trial, 133 patients were recruited in 32 centres in Germany. Patients were randomised 1:1 to second-line chemotherapy either with vinorelbine plus everolimus (arm1) or vinorelbine alone (arm2). Primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS rate at 6 months, overall survival (OS), overall response rate (ORR) and safety. Baseline PI3 K mutational status was determined in plasma samples. RESULTS:Median progression-free survival was not different between arms (arm1 vs. arm2: 4.01 months, 95% CI 2.40-6.09 vs. 4.08, 95% CI 2.80-5.33). PFS rate at 6 months (arm1 vs. arm2: 39.4%, 95% CI 27.6-50.9% vs. 36.6%, 95% CI 24.6-48.6%), median OS (arm1 vs. arm2: 16.3 months, 95% CI 11.4-19.0 vs. 13.8 months, 95% CI 10.2-19.1) and ORR were not different between arms. Most frequent grade 3/4 adverse events were neutropenia (50% vs. 40%), gastrointestinal toxicities (19.1% vs. 6.1%), and infections (19.1% vs. 7.7%). PI3 K mutational status was neither associated with PFS nor with OS. CONCLUSION: Although well tolerated, the efficacy of everolimus and vinorelbine combination therapy was not superior to vinorelbine monotherapy. There was no correlation between PI3 K mutational status and efficacy. EudracCT No 2011-001024-38, ClinicalTrials.gov No NCT01520103.
RCT Entities:
PURPOSE: Improving the outcome of patients with HER2-negative metastatic breast cancer experiencing tumour progression following first-line chemotherapy remains an urgent medical need. The purpose of the VicTORia trial was to show superiority of everolimus in combination with vinorelbine versus vinorelbine monotherapy as second-line chemotherapy for patients with advanced HER2 negative breast cancer. METHODS: In this randomised phase II trial, 133 patients were recruited in 32 centres in Germany. Patients were randomised 1:1 to second-line chemotherapy either with vinorelbine plus everolimus (arm1) or vinorelbine alone (arm2). Primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS rate at 6 months, overall survival (OS), overall response rate (ORR) and safety. Baseline PI3 K mutational status was determined in plasma samples. RESULTS: Median progression-free survival was not different between arms (arm1 vs. arm2: 4.01 months, 95% CI 2.40-6.09 vs. 4.08, 95% CI 2.80-5.33). PFS rate at 6 months (arm1 vs. arm2: 39.4%, 95% CI 27.6-50.9% vs. 36.6%, 95% CI 24.6-48.6%), median OS (arm1 vs. arm2: 16.3 months, 95% CI 11.4-19.0 vs. 13.8 months, 95% CI 10.2-19.1) and ORR were not different between arms. Most frequent grade 3/4 adverse events were neutropenia (50% vs. 40%), gastrointestinal toxicities (19.1% vs. 6.1%), and infections (19.1% vs. 7.7%). PI3 K mutational status was neither associated with PFS nor with OS. CONCLUSION: Although well tolerated, the efficacy of everolimus and vinorelbine combination therapy was not superior to vinorelbine monotherapy. There was no correlation between PI3 K mutational status and efficacy. EudracCT No 2011-001024-38, ClinicalTrials.gov No NCT01520103.
Entities:
Keywords:
Everolimus; HER2 negative; Metastatic breast cancer; Second-line treatment; Vinorelbine
Authors: Aleksandr Ianevski; Jenni Lahtela; Komal K Javarappa; Philipp Sergeev; Bishwa R Ghimire; Prson Gautam; Markus Vähä-Koskela; Laura Turunen; Nora Linnavirta; Heikki Kuusanmäki; Mika Kontro; Kimmo Porkka; Caroline A Heckman; Pirkko Mattila; Krister Wennerberg; Anil K Giri; Tero Aittokallio Journal: Sci Adv Date: 2021-02-19 Impact factor: 14.136