Phase III Trial Did Not Show Superiority of Eribulin Compared With Capecitabine in Metastatic Breast Cancer

This abstract will be presented at a press conference hosted by C. Kent Osborne, M.D., director of the Lester and Sue Smith Breast Cancer Center at Baylor College of Medicine, on Friday, Dec. 7 at 7:30 a.m. CT in Room 217 A-C of the Henry B. Gonzales Convention Center. Reporters who cannot attend in person can call in using the following information:• U.S./Canada (toll free): 1 (800) 446-2782• International (toll call): 1 (847) 413-3235

Newswise — SAN ANTONIO — A phase III multicenter study of eribulin mesylate in women with previously treated metastatic breast cancer failed to meet its co-primary endpoints of improved progression-free survival and overall survival compared with capecitabine, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

“The study did not show a statistically significant benefit of eribulin over capecitabine, and it did not show a benefit in terms of progression-free survival, so the overall study objectives were not met,” said Peter A. Kaufman, M.D., associate professor of medicine at the Geisel School of Medicine at Dartmouth and the Norris Cotton Cancer Center in Lebanon, N.H.

“However, this is the first study demonstrating that eribulin is active in the first-, second- and third-line setting in metastatic breast cancer,” Kaufman said. “Although we didn’t show a statistically significant superiority over capecitabine, which was our goal, numerically the overall survival with eribulin was better than with capecitabine.”

In 2010, the FDA approved eribulin for the treatment of patients with metastatic breast cancer who had previously received an anthracycline and a taxane and at least two cytotoxic chemotherapy treatment regimens for metastatic breast cancer. The FDA granted approval based on data showing a statistically significant improvement in overall survival compared with current treatments.

Kaufman and colleagues examined whether eribulin would be effective as an earlier-line treatment in women with metastatic breast cancer. They randomly assigned 1,102 patients to eribulin or capecitabine. Patients had all received prior anthracycline- and taxane-based therapy and received the study drug as the first, second or third line of therapy for metastatic disease.

The median overall survival for patients assigned to eribulin was 15.9 months compared with 14.5 months for patients assigned to capecitabine. Median progression-free survival was 4.1 months for eribulin and 4.2 months for capecitabine.

Exploratory analyses of patient subsets showed that the median overall survival in women with HER2-negative breast cancer was 15.9 months with eribulin compared with 13.5 months with capecitabine. In women with triple-negative breast cancer, which is a particularly aggressive subset, the median overall survival was 14.4 months with eribulin compared with 9.4 months with capecitabine.

Kaufman and colleagues are still compiling data from the quality-of-life analysis, which according to Kaufman, will help guide their next steps in further studying eribulin in this patient population.

“Although we did not meet our primary endpoints, this is still the first study demonstrating the activity of eribulin in earlier lines of treatment of metastatic breast cancer,” Kaufman said. “Eribulin is an active therapy in this setting, and overall, it has potentially comparable activity to capecitabine, which is a widely used treatment in this patient population.”

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The mission of the 2012 CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

Abstract:Publication Number: S6-6

Title: A Phase III, open-label, randomized, multicenter study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes

Peter A Kaufman1, Ahmad Awada2, Christopher Twelves3, Louise Yelle4, Edith Perez5, Jantien Wanders6, Martin S Olivo7, Yi He7, Corina E Dutcus7 and Javier Cortes8. 1Breast Oncology (Section of Hematology/Oncology), Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 2Medical Oncology Clinic, Jules Bordet Institute, Brussels, Belgium; 3Leeds Institute of Molecular Medicine and St James's Institute of Oncology, Leeds, United Kingdom; 4Department of Medicine, University of Montreal, Montreal, Canada; 5Mayo Medical Clinic, Jacksonville, FL; 6Eisai Ltd., Hatfield, United Kingdom; 7Eisai Inc., Woodcliff Lake, NJ and 8Vall D'Hebron University Hospital, Barcelona, Spain.

Background: Eribulin is a non-taxane microtubule dynamics inhibitor. In a previous Phase III trial, eribulin demonstrated a statistically significant improvement in overall survival (OS) versus current treatments and a manageable toxicity profile, in heavilypre-treated patients (pts) with metastatic breast cancer (MBC). Here we report results from a Phase III trial of eribulin compared with capecitabine in earlier-line pts with MBC (NCT00337103).

Patients and methods: Pts were randomized 1:1 to eribulin mesylate 1.4 mg/m2 given on Days 1 and 8 of a 21 day cycle or capecitabine 2.5 g/m2/day administered orally BID on Days 1 to 14 of a 21 day cycle. Eligible pts had received prior therapy including an anthracycline and taxane, and were receiving study drug as 1st, 2nd, or 3rd line therapy for advanced disease. The co-primary endpoints of this study were OS and progression free survival (PFS): pre-specified statistical significance at final analysis for eribulin versus capecitabine were p≤0.0372 for OS and p<0.01 for PFS. Secondary endpoints included objective response rate (ORR), quality of life (QoL) measured using the EORTC questionnaire, duration of response, 1-, 2- and 3-year survival, and safety. The study was stratified for geographic region and HER2 status.

Results: Of 1102 pts, 554 were randomized to eribulin and 548 capecitabine (375 and 380 pts were HER2[-], respectively). The median age was 54.0 years (range 24-80). Pts received study treatment as their 1st (27.2%), 2nd (57.4%) or 3rd-line (14.7%) chemotherapeutic regimen in the setting of metastatic disease. The median number of treatment cycles was 6 for eribulin and 5 for capecitabine. Median OS was 15.9 and 14.5 months (hazard ratio [HR] 0.879; 95% confidence intervals [CI] 0.770-1.003;p=0.056), and PFS (independent review) was 4.1 and 4.2 months (HR 1.079; 95% CI 0.932-1.250; p=0.305) for eribulin and capecitabine, respectively. ORR (independent review) were 11.0% (95% CI 8.5-13.9) and 11.5% (95% CI 8.9-14.5; p=0.849), respectively. OS for HER2(-) pts was 15.9 months for eribulin and 13.5 months for capecitabine (HR 0.838; 95% CI 0.715-0.983; p=0.030). AEs were consistent with the known side-effect profiles of both drugs. The most common AEs for eribulin and capecitabine (>20% all grades) were neutropenia (54.2% vs 15.9%), hand-foot syndrome (0.2% vs 45.1%) alopecia (34.6% vs 4.0%), leukopenia (31.4% vs 10.4%), diarrhea (14.3% vs 28.8%), and nausea (22.2% vs 24.4%), respectively.

Conclusion: In this Phase III trial, eribulin demonstrated a trend favoring improved OS, compared with capecitabine, although this improvement does not meet the pre-defined criteria for statistical significance. This study confirms eribulin as an active drug in pts with MBC, and exploratory analyses suggest possible benefits of eribulin in specific subsets of pts, sufficient to warrant further study.