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Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial

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Abstract

Patients with metastatic triple-negative breast cancer (TNBC) typically have a poor prognosis and limited treatment options. To determine the impact of combining bevacizumab with second-line chemotherapy in patients with metastatic TNBC, we performed an exploratory subgroup analysis of the randomized phase 3 RIBBON-2 trial. RIBBON-2 enrolled patients with metastatic breast cancer that had progressed on first-line non-bevacizumab-containing chemotherapy. After selection of chemotherapy (taxane, gemcitabine, capecitabine, or vinorelbine), patients were randomized 2:1 to receive chemotherapy with either bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Of 684 patients treated in RIBBON-2, 159 (23%) had TNBC. Baseline characteristics were reasonably balanced in the two treatment groups. The majority received taxane chemotherapy. The hazard ratio (HR) for PFS was 0.494 [95% confidence interval (CI) 0.33–0.74; P = 0.0006]. Median PFS was 6.0 months with bevacizumab–chemotherapy versus 2.7 months with chemotherapy alone. Median OS was 17.9 versus 12.6 months, respectively (HR 0.624, 95% CI 0.39–1.007; P = 0.0534). ORR was 41 versus 18%, respectively (P = 0.0078). The safety profile was consistent with the overall study population and previous phase 3 trials of bevacizumab. Patients with metastatic TNBC derived significant PFS and response benefits from the combination of bevacizumab with second-line chemotherapy. Despite the small sample size and immature data, there was a trend toward improved OS.

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Acknowledgments

The RIBBON-2 trial was sponsored and funded by Genentech Inc., South San Francisco, CA, USA. The sponsor contributed to the study design and performed the statistical analyses. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd.

Conflict of interest

A. Brufsky has a Consultant/advisory role with Genentech. V. Valero has received research funding and honoraria from Genentech/Roche. H.S. Rugo’s institution has received research funding from Genentech/Roche and Lilly/Imclone. A. Duenne is an employee of F. Hoffmann-La Roche Ltd. N. Bousfoul was formerly a contractor for F. Hoffmann-La Roche Ltd. The other authors have no conflict of interest to declare.

Ethical standards

RIBBON-2 was conducted in accordance with US Food and Drug Administration Good Clinical Practice, International Conference on Harmonisation E6 Guideline for Good Clinical Practice, and national and local ethical and legal requirements. All patients provided written informed consent before study-specific screening.

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Authors and Affiliations

  1. Magee Women’s Hospital, University of Pittsburgh School of Medicine, 300 Halket Street, Suite 4628, Pittsburgh, PA, 15213, USA

    Adam Brufsky

  2. The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1354, Houston, TX, 77030, USA

    Vicente Valero

  3. Philippine General Hospital, Manila, Philippines

    Beatrice Tiangco

  4. Wichita Community Clinical Oncology Program, Wichita, KS, USA

    Shaker Dakhil

  5. Latvian Oncology Center, Riga Eastern University Hospital, Riga, Latvia

    Arija Brize

  6. University of California San Francisco Helen Diller Family Comprehensive Cancer Center, 1600 Divisidero Street, 2nd Floor, San Francisco, CA, 94115, USA

    Hope S. Rugo

  7. US Oncology, El Paso, TX, USA

    Ragene Rivera

  8. F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland

    Anja Duenne & Naima Bousfoul

  9. Sarah Cannon Research Institute, Nashville, TN, USA

    Denise A. Yardley

  10. Tennessee Oncology PLLC, Nashville, TN, USA

    Denise A. Yardley

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  1. Adam Brufsky
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Correspondence to Adam Brufsky.

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Brufsky, A., Valero, V., Tiangco, B. et al. Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial. Breast Cancer Res Treat 133, 1067–1075 (2012). https://doi.org/10.1007/s10549-012-2008-6

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  • DOI: https://doi.org/10.1007/s10549-012-2008-6

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