Journal Article

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial

Vetter, Marcus, Küng, Marc, Trojan, Andreas, Rochlitz, Christoph, Hasler-Strub, Ursula, Bigler, Martin, Borner, Markus, Zaman, Khalil, Rauch, Daniel, Müller, Andreas, Bärtschi, Daniela, Cathomas, Richard, Bernhard, Jürg, Matter-Walstra, Klazien, Ruhstaller, Thomas, Wicki, Andreas, Rordorf, Tamara, Na, Kyung-Jae, von Moos, Roger, Anchisi, Sandro, Winterhalder, Ralph

2016

Overview

Background Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. Methods This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3–5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. Results Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15–35 %) and arm B (24 % [16/68]; 95 % CI 13–34 %; P  = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46–0.69) and 50 % (37/74; 95 % CI 0.39–0.61) in arms A and B, respectively ( P  = 0.45). Median PFS was 10.3 months (95 % CI 8.7–11.3) in arm A and 8.5 months (95 % CI 6.5–11.9) in arm B ( P  = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. Conclusion This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3–5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Administration, Metronomic / Adult / Aged / Aged, 80 and over / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Bevacizumab - administration & dosage / Biomarkers, Tumor / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - metabolism / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Cancer Research / Cancer therapies / Capecitabine - administration & dosage / Care and treatment / Chemotherapy / Comparative analysis / Complications and side effects / Cyclophosphamide / Cyclophosphamide - administration & dosage / Dosage and administration / Drug withdrawal / FDA approval / Female / Health Promotion and Disease Prevention / Humans / Male / Medical and radiation oncology / Medicine/Public Health / Metastasis / Middle Aged / Neoplasm Metastasis / Neoplasm Staging / Neutropenia / Oncology / Paclitaxel / Paclitaxel - administration & dosage / Patients / Quality of Life / Questionnaires / Receptor, ErbB-2 - metabolism / Research Article / Retreatment / Surgical Oncology / Toxicity / Treatment Outcome