Abstract 203P
Background
Single-agent chemotherapy (CT) is a valuable option for patients with advanced breast cancer (ABC) and weekly oral VNR is one of the recommended agents. Metronomic VNR increases patient’s exposure to the drug while improving safety. In early studies, minimal toxicity and promising efficacy were observed with metronomic VNR 50 mg thrice weekly (tw). We randomized patients with ABC to receive either metronomic or weekly oral first-line VNR.
Methods
Open-label, multicentre, randomized phase II study evaluating Disease Control Rate (DCR) as primary endpoint in patients previously untreated with CT for HR+/HER2- ABC, pretreated with endocrine-therapy (ET) and no longer candidates to further ET. Arm A: Metronomic VNR 50 mg tw, Arm B: VNR 60 mg/m2 weekly at cycle 1, increased to 80 mg/m2 weekly for subsequent cycles in the absence of grade 3-4 neutropenia, until progression or intolerance.
Results
163 patients included (82 in arm A, 81 in arm B): 86% had ≥ 2 organs involved and 63% had previous 1-2 lines of ET. Relative dose intensity ≥ 90% per patient (pt) was 58.5% in arm A and 29% in arm B. Primary endpoint was reached in both arms with DCR of 63.4% [95% CI: 52.0; 73.8] in arm A and 72.8% [95% CI: 61.8; 82.1] in arm B, respectively. Median PFS was 4.0 [95% CI: 2.8; 5.4] and 5.6 [95% CI: 4.4; 7.8] months in arm A and arm B, respectively. Median overall survival was 22.3 months [95% CI: 19.0; 27.3] in Arm A and 26.7 months [95% CI: 22.2; 37.8] in arm B. Grade 3-5 adverse events were 31% in arm A and 60% in arm B, including 24% versus 51% of neutropenia, and 0% versus 2.5% of febrile neutropenia, respectively. We observed less gastrointestinal toxicity in arm A than in arm B: 46% versus 73%, any grade. Two toxic deaths were observed in each arm (2 sepsis, 1 enterocolitis, 1 cardiac failure).
Conclusions
Although the study was not comparative, PFS and OS were numerically higher in the weekly arm, while tolerance and dose intensity were better in the metronomic arm, suggesting “peak effect”. Awaiting the results of other ongoing randomized studies in combination or later lines, weekly single agent VNR should be preferred over metronomic single agent VNR in first line CT after progression on ET in HR+ ABC pts.
Clinical trial identification
EudraCT 2014-003860-19.
Editorial acknowledgement
An editorial assistance in the writing of the abstract was provided by Nicole Fort, Medical Oncology. The authors thank all investigators and coinvestigators who could not be listed as authors, all study teams of all participating centers, nurses, patients and their families for participation in the study.
Legal entity responsible for the study
Pierre Fabre Médicament.
Funding
Pierre Fabre Médicament.
Disclosure
M.E. Cazzaniga: Financial Interests, Institutional, Advisory Board: Lilly. N. Martinez Jañez: Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Expert Testimony: Sankyo; Financial Interests, Institutional, Expert Testimony: Pfizer; Financial Interests, Institutional, Expert Testimony: Novartis; Financial Interests, Institutional, Expert Testimony: Lilly; Financial Interests, Institutional, Expert Testimony: Pierre Fabre; Financial Interests, Institutional, Expert Testimony: Roche; Financial Interests, Institutional, Expert Testimony: GSK; Financial Interests, Institutional, Other, Travel Support: Roche; Financial Interests, Institutional, Other, Travel Support: AstraZeneca; Financial Interests, Institutional, Other, Travel Support: Novartis; Financial Interests, Institutional, Other, Travel Support: Pfizer. M. Muñoz Mateu: Financial Interests, Institutional, Expert Testimony: Roche; Financial Interests, Institutional, Expert Testimony: Novartis; Financial Interests, Institutional, Expert Testimony: Eisai; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Lilly. L. Cortesi: Financial Interests, Institutional, Other, Honororia: AstraZeneca; Financial Interests, Institutional, Other, Honororia: MSD; Financial Interests, Institutional, Other, Honororia: Pfizer; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Tesaro; Financial Interests, Institutional, Advisory Role: Clovis. M. Palacova: Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Expert Testimony: Novartis; Financial Interests, Institutional, Expert Testimony: Pfizer; Financial Interests, Institutional, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Expert Testimony: Amgen. E. Petru: Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Expert Testimony: Sankyo; Financial Interests, Institutional, Expert Testimony: Pfizer; Financial Interests, Institutional, Expert Testimony: Novartis; Financial Interests, Institutional, Expert Testimony: Lilly; Financial Interests, Institutional, Expert Testimony: Pierre Fabre; Financial Interests, Institutional, Expert Testimony: Roche; Financial Interests, Institutional, Expert Testimony: GSK; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, Travel Support: AstraZeneca; Financial Interests, Institutional, Other, Travel Support: GSK; Financial Interests, Institutional, Other, Travel Support: Pfizer; Financial Interests, Institutional, Other, Travel Support: Lilly. J. Ettl: Financial Interests, Institutional, Expert Testimony: AstraZeneca; Financial Interests, Institutional, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Expert Testimony: Sankyo; Financial Interests, Institutional, Expert Testimony: Pfizer; Financial Interests, Institutional, Expert Testimony: Novartis; Financial Interests, Institutional, Expert Testimony: Lilly; Financial Interests, Institutional, Expert Testimony: Pierre Fabre; Financial Interests, Institutional, Expert Testimony: Roche; Financial Interests, Institutional, Expert Testimony: Tesaro; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Odenate; Financial Interests, Institutional, Other, Travel Support: AstraZeneca; Financial Interests, Institutional, Other, Travel Support: Daiichi Sankyo; Financial Interests, Institutional, Other, Travel Support: Celgene; Financial Interests, Institutional, Other, Travel Support: Pfizer; Financial Interests, Institutional, Other, Travel Support: Novartis; Financial Interests, Institutional, Other, Travel Support: Lilly; Financial Interests, Institutional, Other, Travel Support: Tesaro. C. De Almeida: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre. R. Raymond: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre Médicament. G.R. Villanova: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre. C. Ta Thanh Minh: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre. A.C.F. Rodrigues: Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Training: Pfizer; Financial Interests, Institutional, Training: AstraZeneca. G. Freyer: Financial Interests, Institutional, Principal Investigator: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Pierre Fabre. All other authors have declared no conflicts of interest.