Single-agent metronomic versus weekly oral vinorelbine as first-line chemotherapy in patients with HR-positive/HER2-negative advanced breast cancer: The randomized Tempo Breast study
Gilles Freyer,
Noelia Martinez-Jañez,
Bożena Kukielka-Budny,
Malgorzata Ulanska,
Hugues Bourgeois,
Montserrat Muñoz,
Serafin Morales,
Juan Bayo Calero,
Laura Cortesi,
Tamás Pintér,
Markéta Palácová,
Nelli Cherciu,
Edgar Petru,
Johannes Ettl,
Cécilia de Almeida,
Gustavo Villanova,
Romain Raymond,
Christine Ta Thanh Minh,
Ana Rodrigues,
Marina E. Cazzaniga
Affiliations
Gilles Freyer
Medical Oncology Department, Institut de Cancérologie des HCL, 165 chemin du Grand Revoyet, 69495 Pierre-Bénite & Université de Lyon, Lyon, France; Corresponding author.
Noelia Martinez-Jañez
Oncology Department, Hospital Universitario Ramón y Cajal, Carretera De Colmenar Viejo km. 9,1, 28034 Madrid, Spain
Bożena Kukielka-Budny
Oncology Department, Centrum Onkologii Ziemi Lubelskiej, Ul. Jaczewskiego 7, 20-090 Lublin, Poland
Malgorzata Ulanska
Oncology Department, Centrum Terapii Wspolczesnej, Ul. Kopcinskiego 21, 90-242 Łódź, Poland
Hugues Bourgeois
Oncology Department, Centre Jean-Bernard, 9 rue Beauverger, 72015 Le Mans, France
Montserrat Muñoz
Oncology Department, Hospital Clinic i Provincial de Barcelona, 170 Esc.2, pl. 5a, 08036 Barcelona, Spain
Oncology Department, SC Oncolab SRL, Str. Bujorului, Nr. 7, 200385 Craiova, Romania
Edgar Petru
Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz, 15, 8036 Graz, Austria
Johannes Ettl
Department of Obstetrics and Gynecology, Klinikum Rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany
Cécilia de Almeida
Pierre Fabre Medicament, Medical & Patient/Consumer Department, 33 Av. Emile Zola, 92100 Boulogne Billancourt, France
Gustavo Villanova
Pierre Fabre Medicament, Medical & Patient/Consumer Department, 33 Av. Emile Zola, 92100 Boulogne Billancourt, France
Romain Raymond
Pierre Fabre Medicament, Medical & Patient/Consumer Department, 33 Av. Emile Zola, 92100 Boulogne Billancourt, France
Christine Ta Thanh Minh
Pierre Fabre Medicament, Medical & Patient/Consumer Department, 33 Av. Emile Zola, 92100 Boulogne Billancourt, France
Ana Rodrigues
Oncology Department, Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE, Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
Marina E. Cazzaniga
Phase 1 Clinical Research Unit, ASST Monza, via Pergolesi 33, 20052 Monza, Italy; Medical Oncology, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126, Milan, Italy
Introduction: Single-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce. Methods: In this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more). Results: One-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0–73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8–82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events. Conclusions: In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule. Clinical trial registration number: EudraCT 2014-003860-19.
