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BMC Cancer. 2016 Oct 10;16(1):780.

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.

Author information

1
Department of Oncology, University Hospital Basel, Petersgraben 4, Basel, CH-4031, Switzerland. Christoph.Rochlitz@usb.ch.
2
SAKK Coordinating Center, Bern, Switzerland.
3
Department of Oncology, Kantonsspital Graubünden, Chur, Switzerland.
4
International Breast Cancer Study (IBCSG) and Inselspital, Bern University Hospital, Bern, Switzerland.
5
SAKK Coordinating Center, Bern, Switzerland and European Center for Pharmaceutical Medicine, University Basel, Basel, Switzerland.
6
Department of Oncology, University Hospital Basel, Petersgraben 4, Basel, CH-4031, Switzerland.
7
Department of Oncology, University Hospital Lausanne, Lausanne, Switzerland.
8
Department of Oncology, Hospital of Valais, Sion, Switzerland.
9
Department of Oncology, Kantonsspital Fribourg, Fribourg, Switzerland.
10
Present Address: Novartis Pharma, Stein, Switzerland.
11
Department of Oncology, Spitalzentrum Biel, Biel, Switzerland.
12
Department of Oncology, University Hospital Zürich, Zürich, Switzerland.
13
Department of Oncology, Spital STS, Thun, Switzerland.
14
Department of Oncology, Kantonsspital Winterthur, Winterthur, Switzerland.
15
Department of Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
16
Department of Oncology, OnkoZentrum Zürich, Zürich, Switzerland.
17
Luzerner Kantonsspital, Luzerne, Switzerland.

Abstract

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.

KEYWORDS:

Bevacizumab; Breast cancer; Metronomic chemotherapy; Toxicity

PMID:
27724870
PMCID:
PMC5057418
DOI:
10.1186/s12885-016-2823-y
[Indexed for MEDLINE]
Free PMC Article

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