Abstract S3-04: The phase III ICE study: Adjuvant Ibandronate with or without capecitabine in elderly patients with moderate or high risk early breast cancer

Abstract

Abstract Background: Although approximately 50% of newly diagnosed breast cancers arise in women above 65 years old they are underrepresented in clinical trials. The ICE study was designed to investigate if a mono-chemotherapy with capecitabine in addition to the third generation bisphosphonate ibandronate will improve the outcome compared to ibandronate alone in elderly breast cancer patients with medium and high risk primary breast cancer not suitable for standard chemotherapy. Methods: This is a prospective, multi-center, controlled, open-label, randomized phase III trial. Female patients ≥ 65 years with unilateral or bilateral breast cancer who are either node-positive or high-risk node-negative (tumor size ≥2 cm, grade >I, and/or ER-and PR-negative); and a Charlson Comorbidity Index (CMI) ≤2 received either ibandronate alone for 2 years, 50 mg p.o. daily alternatively 6 mg i.v. every 4 weeks or the same ibandronate regimen together with capecitabine 2000 mg/m2 on day 1 – 14 q day 22 for 6 cycles to be started within 6 months after axillary dissection. Patients with hormone-sensitive disease received an endocrine therapy according to guidelines. The primary objective is disease-free survival. A total of 1,394 patients were needed (5-year DFS improvement from 65% with ibandronate to 71.5% with ibandronate/capecitabine; α=0.05, ß=80%) and we expected 497 events during a median 5 year follow up. Results: Between 06/2004 and 08/2008, 1409 patients were randomized to ibandronate (N=702) or ibandronate/capecitabine (N=668) in 172 German centers, of whom 1380 patients started treatment (689 and 691 respectively). Median age was 71 (range 74-80) years; 58.6% of patients had a CMI≥1, 48.2% had N+, 35.2% grade 3, and 19.2% had ER/PgR negative disease. 83.8% of patients received all 6 capecitabine cycles. Capecitabine grade 3/4 toxicities were <2% except hand-foot-syndrome (6.8%). 3 patients died in relation with capecitabine treatment. Final DFS analysis will be presented at the meeting. Conclusion: CALGB 49907 showed that AC or CMF was superior to capecitabine in patients aged ≥65 years but was associated with twice as many moderate to severe toxic effects (64% vs 33%) (Muss H et al, NEJM 2012). The ICE study will provide evidence if capecitabine monotherapy is as active as adjuvant treatment and if it might be an option for frail and/or elderly patients where standard chemotherapy is considered to be too toxic. Citation Format: Gunter von Minckwitz, Toralf Reimer, Jochen Potenberg, Bettina Conrad, Ulrike Schürer, Holger Eidtmann, Marianne Just, Stefan Paepke, Elmar Stickeler, Georg Heinrich, Michael Untch, Volker Moebus, Christoph Thomssen, Christian Jackisch, Jens Huober, Sibylle Loibl, Valentina Nekljudova, Ulrike Nitz. The phase III ICE study: Adjuvant Ibandronate with or without capecitabine in elderly patients with moderate or high risk early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-04.