August 2010, Vol 3, No 5 by The Oncology Nurse

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ASCO Highlights BREAST CANCER

Novel Agents Improve Survival in Refractory Metastatic Breast Cancer CHICAGO—Several new agents elicited excitement for the treatment of women with advanced breast cancer, including a novel cytotoxic agent that is the first to improve survival as monotherapy in this challenging patient population. In an international study, patients with metastatic breast cancer refractory to numerous treatments lived 2.5 months longer when treated with eribulin mesylate, a synthetic analog of the novel halichondrin B family, versus single agents alone. Principal investigator Christopher Twelves, MD, of the University of Leeds in the United Kingdom, said, “The improvement is statistically significant and clinically meaningful for these women with a poor prognosis.” The Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice versus Eribulin (EMBRACE) was a global, randomized, open-label phase 3 trial involving 762 metastatic breast cancer patients who had received a median of four prior chemotherapy regimens. Most were estrogen receptor–positive and human epidermal growth factor receptor type 2 (HER2)negative, and about half had two or more metastatic sites. Patients were randomized 2:1 to eribulin given intravenously twice a month every 3 weeks or to a treatment of physician’s choice (TPC), which could be any single agent—cytotoxic, endocrine, or biologic—approved for the treatment of cancer. “We allowed physician’s choice because there is no single established standard and we felt it was inappropriate to restrict the options. This was a real-life comparison,” Twelves noted. Overall survival improved by 2.5 months Median overall survival (OS), the primary end point, improved from 10.65 months with standard singleagent therapy to 13.12 months with eribulin, representing a 19% reduction in mortality risk (P = .04). One-year survival was 53.9% with eribulin and 43.7% in the TPC arm. “The benefits were achieved with a manageable toxicity,” Twelves an nounced. Serious adverse events (AEs) were observed in 25% of each arm, and AEs leading to treatment interruption, dose delays, and interruptions and discontinuations were similar. “EMBRACE is the first phase 3 singleagent study in heavily pretreated

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metastatic breast cancer to meet its primary end point of prolonged overall survival, so these are striking findings,” Twelves concluded. “The 2.5-month improvement in median survival represented a 23% benefit. We see these findings as potentially establishing eribulin as a new option.” Eric P. Winer, MD, head of medical oncology at Dana-Farber Cancer Center, Boston, commented at a press briefing that a 2.5-month improvement is “a difference that is sufficient to make one look seriously at this agent.” T-DM1 effective after trastuzumab A small phase 1 trial found that trastuzumab conjugated to DM-1 (TDM1), with or without the monoclonal antibody pertuzumab, was efficacious in women with advanced HER2positive breast cancers who were previously treated with trastuzumab. T-DM1 is a HER2-targeted antibody drug conjugate composed of the cytotoxic agent DM1 (an antimicrotubule agent) conjugated to the monoclonal antibody

By Caroline Helwick

“The 2.5-month improvement in median survival represented a 23% benefit. We see these findings as potentially establishing eribulin as a new option.” —Christopher Twelves, MD

trastuzumab. Pertuzumab is a monoclonal antibody that binds to a different HER2 receptor than T-DM1. The theory is that the use of these agents in combination will offer complementary modes of action that will more fully cover the HER receptors and thus be more effective in treating HER2-overexpressing tumors. The study has so far enrolled 44 patients with advanced or metastatic HER2-positive breast cancers, all of whom had previously received tras tuzumab. Outcomes were reported for 28 of the participants, 10 of whom

had partial responses, for a 36% response rate, when treated with TDM1 and pertuzumab, according to Kathy Miller, MD, of Indiana University, Indianapolis. Edith Perez, MD, the Serene M. and Frances C. Durling Professor of Medicine at the Mayo Clinic, Jacksonville, commented, “The use of two targeted agents in these advanced breast cancer patients is a reasonable approach to therapy.” ● For more ASCO coverage, go to www.theoncologynurse.com/asco.

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AugusT 2010 I VOL 3, NO 5