Adjuvant Bevacizumab Did Not Improve Invasive Disease-free Survival in Triple-negative 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 — Patients who received one year of bevacizumab in addition to chemotherapy for the postsurgical treatment of triple-negative breast cancer had no statistically significant improvement in invasive disease-free survival compared with patients treated with chemotherapy alone, according to the primary results of the phase III BEATRICE study.

“This study did not confirm the hypothesis that adding bevacizumab to chemotherapy would improve patients’ outcomes,” said David Cameron, M.D., professor of oncology at Edinburgh University in Scotland, who presented the results at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8. “Therefore, sadly for patients, we have nothing extra to add to chemotherapy for early, triple-negative breast cancer.”

Prior research has shown that bevacizumab combined with chemotherapy significantly improves progression-free survival in metastatic breast cancer and improves pathologic complete response in the neoadjuvant setting. The dependence of micrometastases on angiogenesis suggested to Cameron and his colleagues that patients might benefit from anti-angiogenic strategies, such as bevacizumab, applied in the adjuvant setting.

In BEATRICE, an open-label, multinational, phase III study, researchers randomly assigned 2,591 patients with triple-negative operable primary invasive breast cancer to four or more cycles of anthracycline-based or taxane-based chemotherapy with or without one year of bevacizumab.

At a median follow-up of 32 months, the hazard ratio for invasive disease-free survival was 0.87 (95% CI 0.72–1.07) in favor of patients assigned to chemotherapy and bevacizumab. Researchers reported 107 deaths among patients who received chemotherapy alone compared with 93 deaths among those who received chemotherapy and bevacizumab. “The findings are reminiscent of what was reported in operable colorectal cancer,” Cameron said. “Bevacizumab clearly does something in this setting, but the effect is not sustained, and therefore, adding bevacizumab to chemotherapy for all these patients is not the way to improve their chances.”

Researchers found no difference in the amount of chemotherapy delivered and found no increase in the risk for fatal adverse events in patients assigned to bevacizumab. However, the addition of bevacizumab to chemotherapy was associated with an increase in grade 3 or worse hypertension, left ventricular dysfunction and congestive heart failure.

“We still need to understand what is special about the biology of breast cancers that do not express hormone receptors, nor overexpress HER2,” Cameron said. “We need to explore which cancers might benefit from other additional therapies, including the possibility that some of them might benefit from drugs like bevacizumab.”

# # #

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: S6-5

Title: Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer

David Cameron1, Julia Brown2, Rebecca Dent3,15, Christian Jackisch4, John Mackey5, Xavier Pivot6, Guenther Steger7, Thomas Suter8, Masakazu Toi9, Mahesh Parmar10, Lida Bubuteishvili-Pacaud11, Volkmar Henschel12, Rita Laeufle13 and Richard Bell14. 1Department of Oncology, University of Edinburgh and Cancer Services, NHS Lothian, Edinburgh, United Kingdom; 2Clinical Trials Research Unit (CTRU), University of Leeds, United Kingdom; 3Department of Medical Oncology, Sunnybrook Health Sciences Center and University of Toronto, Toronto, ON, Canada; 4Department of Obstetrics and Gynecology & Breast Cancer Center, Klinikum Offenbach, Offenbach, Germany; 5Cross Center Institute, Edmonton, Canada; 6Service Oncologie Medicale, University Hospital Jean Minjoz, Besançon, France; 7Department of Internal Medicine, Division of Oncology, Medical University of Vienna, Austria; 8Swiss Cardiovascular Center, Bern University Hospital, Inselspital, Switzerland; 9Faculty of Medicine, Kyoto University, Kyoto, Japan; 10MRC Clinical Trials Unit, London, United Kingdom; 11F. Hoffmann-La Roche Ltd, Basel, Switzerland; 12Biostatistics, F Hoffmann-La Roche Ltd, Basel, Switzerland; 13PDOA, Oncology, F. Hoffmann-La Roche Ltd., Basel, Switzerland; 14Department of Medical Oncology, Andrew Love Cancer Centre, Geelong, Australia and 15Department of Medical Oncology, National Cancer Center, Singapore, Singapore.

Body: Background: Bevacizumab (BEV), an anti-VEGF antibody, significantly enhanced progression-free survival in metastatic breast cancer (BC) (E2100, AVADO, RIBBON-1, RIBBON-2) and pathologic complete response rates in the neoadjuvant setting (GeparQuinto, NSABP B-40) when combined with chemotherapy (CT). The dependence of micro-metastases on angiogenesis [Holmgren 1995] suggests that patients might benefit from anti-angiogenic strategies applied in the adjuvant setting. The BEATRICE trial was designed to test this hypothesis in patients with triple-negative BC, who have a poor prognosis and lack targeted options for treatment.

Methods: In this open-label randomized multinational phase III trial, patients with centrally confirmed triple-negative operable primary invasive BC (pT1a-pT3) were randomized 1:1 after definitive surgery to receive 4 cycles of either CT alone or the same CT + 1 year of BEV 5 mg/kg/wk equivalent. CT was anthracycline [anth] and/or taxane-based. Patients were stratified by nodal status (0 vs 1-3 vs 4 involved nodes), CT backbone (anth vs anth + taxane vs taxane), hormone receptor status (negative vs low), and surgery (breast-conserving vs mastectomy). The primary objective is to compare invasive disease-free survival (IDFS) [Hudis 2007] with adjuvant CT ± 1 year of BEV. Secondary outcome measures are overall survival (OS), breast cancer-free interval, disease-free survival (DFS), distant DFS, and safety (NCI CTCAE v3.0). The sample size was calculated to provide 80% power for a HR=0.75 at =0.05 assuming 5-year IDFS of 72.0% with CT vs 78.2% with CT + BEV with 388 events. BEATRICE also includes evaluation of potential predictive and prognostic biomarkers.

Results: Between Dec 2007 and Mar 2010, 2591 patients were randomized. At data cut-off (Feb 29, 2012), median follow-up was 32 months.

The mean CT exposure was balanced between treatment arms. Median BEV duration was 11.7 months. BEV was associated with an increased incidence of grade 3 congestive heart failure/left ventricular dysfunction (3% vs <1% with CT), grade 3 hypertension (12% vs <1%), and treatment discontinuation (BEV and/or CT: 20% vs 2%) but no increase in the risk of fatal adverse events (0.3% vs 0.2%). No new safety signals were observed.

Conclusion: There was no statistically significant improvement in IDFS with the addition of 1 year's BEV to adjuvant CT for triple-negative BC. Further follow-up is required to assess the impact of BEV on OS. The safety profile was consistent with previous reports in metastatic BC with a low incidence of fatal adverse events. Protocol-specified biomarker analyses are ongoing. Updated OS results are expected in 2013.