Chemotherapeutics in Metastatic Breast Cancer

Panelists: Kimberly L. Blackwell, MD, Duke; Adam M. Brufsky, MD, PhD, University of Pittsburgh;
Joyce A. O’Shaughnessy, MD, US Oncology; Mark D. Pegram, MD, Stanford;
Hope S. Rugo, MD, UCSF; Denise A. Yardley, MD, Sarah Cannon
Published Online: Monday, June 9, 2014
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In January 2005, the FDA approved nab-paclitaxel (Abraxane) for the treatment of patients with metastatic breast cancer following progression on other chemotherapies. Since it’s approval, numerous studies have explored different dosing strategies with nab-paclitaxel, notes Hope S. Rugo, MD.

In the phase III CALGB 40502, nab-paclitaxel at 150 mg/m2 was compared to paclitaxel and ixabepilone. However, at doses of 150 mg/m2 the side effects were difficult to manage, remarks Rugo. Additionally, a clear subset of patients who benefited more from nab-paclitaxel was not identified. At this point the optimal dose remains 100 mg/m2, with studies ongoing that are looking at 125 mg/m2 doses, Rugo notes.

One of these studies (tnAcity) is evaluating the addition of nab-paclitaxel to gemcitabine and carboplatin as a treatment for patients with metastatic triple-negative breast cancer (TNBC), Denise A. Yardley, MD, notes. This phase II/III study plans to collect biomarkers and explore the risk—benefit ratio of the combination before moving onto the phase III portion of the study. Past research has suggested that Src may be a biomarker in select subtypes of TNBC; however, results from tnAcity remain to be seen, notes Yardley.

In 2010, the FDA approved eribulin mesylate (Halaven) for the treatment of patients with metastatic breast cancer following an anthracycline and a taxane. This approval was based on data from the phase III EMBRACE trial that demonstrated a statistically significant improvement in overall survival (OS) in patients receiving eribulin compared to physician's choice of treatment. In the study, the median OS was 13.1 months with eribulin versus 10.6 months in the control group.

Treatment with eribulin requires a 5-minute infusion, which is much shorter than other cytotoxic agents, notes Kimberly L. Blackwell, MD. Additionally, a phase III study demonstrated similar efficacy for eribulin and capecitabine in the first-, second, and third-line. Moreover, subgroup analyses from this trial suggest eribulin may be more active in patients with TNBC compared with capecitabine, Blackwell notes.

It is important to properly manage the side effects with eribulin, notes Rugo. As long as the neuropathy and neutropenia is controlled, the drug is very well tolerated. Additionally, Yardley notes, studies have explored this agent in combination with trastuzumab. These studies demonstrated promising results for the combination. 
View More From This Discussion
Episode 1 Overview of HER2-Targeted Therapies in Breast Cancer
Episode 2 Treating Low-Risk HER2-Positive Breast Cancer
Episode 3 Frontline Pertuzumab for Metastatic Breast Cancer
Episode 4 PIK3CA Mutations in HER2-Positive Breast Cancer
Episode 5 T-DM1 in HER2-Positive Metastatic Breast Cancer
Episode 6 Recommendations for Optimal HER2 Testing in Breast Cancer
Episode 7 Role of Lapatinib in HER2-Positive Breast Cancer
Episode 8 Novel Drug Development in Breast Cancer
Episode 9 Phase III Clinical Trials in HER2-Positive Breast Cancer
Episode 10 Case Study: HER2-Positive Oligometastatic Breast Cancer
Episode 11 Upfront Treatment of HR-Positive MBC
Episode 12 Next Steps for Everolimus in Metastatic Breast Cancer
Episode 13 CDK4/6 Inhibitors in Metastatic Breast Cancer
Episode 14 Chemotherapeutics in Metastatic Breast Cancer
Episode 15 Preventing Skeletal-Related Events in Breast Cancer
Episode 16 Conclusion: Future Direction of Breast Cancer Treatment
Expert Panelists
Dr Adam Brufsky

Adam M. Brufsky, MD, PhD

Professor of Medicine, University of Pittsburgh
Medical Director of the Women’s Cancer Center at Magee-Womens Hospital of UPMC and the University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania

Kimberly L. Blackwell, MD

Professor of Medicine
Assistant Professor in Radiation Oncology
Duke Cancer Institute
Durham, North Carolina

Joyce A. O’Shaughnessy, MD

Co-Director, Breast Cancer Research
Baylor Charles A. Sammons Cancer Center
Texas Oncology, PA/US Oncology,
Dallas, Texas

Mark D. Pegram, MD

Professor of Medicine (Oncology)
Stanford University Medical Center;
Susy Yuan-Huey Hung Professor;
Associate Director of Clinical Research and Director, Breast Cancer Program, Stanford Cancer Institute, Stanford, California

Hope S. Rugo, MD

Professor of Medicine and Director of the Breast Oncology, Clinical Trials, and Education Program, University of California San Francisco Comprehensive Cancer Center, San Francisco, California

Denise A. Yardley, MD

Senior Investigator, Breast Cancer Research
Sarah Cannon Research Institute, Tennessee Oncology, Nashville, Tennessee
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