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

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.

Five‐year results of a phaseIItrial of preoperative 5‐fluorouracil, epirubicin, cyclophosphamide followed by docetaxel with capecitabine (wTX) (with trastuzumab inHER2‐positive patients) for patients with stageIIorIIIbreast cancer

“…In elderly patients, the CALGB 49907 trial compared standard adjuvant therapy with either cyclophosphamide/methotrexate/fluorouracil (CMF) or AC versus capecitabine monotherapy and found that capecitabine had inferior efficacy with regard to both 3‐year RFS and OS . Similarly in the ICE trial, also in a population of elderly patients with breast cancer, no advantage in either 5‐year DFS or OS was observed with the addition of capecitabine to adjuvant therapy with ibandronate alone .…”

Modern methods of treatment of breast cancer in the elderly

“…Отмечено, что трастузумаб может вызвать сердечную недостаточность [25]. Комбинация режимов трастузумаба с доцетакселом и карбоплатином сходна по эффективности с трастузумабом и антрациклинсодержащей ХТ, но ассоциируется с меньшей сердечной токсичностью [26][27][28]. Однако также имеются данные о кардиотоксичности антрациклинов, в то время как безантрациклиновые схемы могут быть использованы без серьезного риска осложнений сердечно-сосудистый системы у пожилых.…”

“…В другом исследовании (Ibandronate and Capecitabine in Elderly Women -ICE) 1358 больных РМЖ в возрасте 65 лет и старше были рандомизированы для получения ибандроната в течение 2 лет и получения ибандроната (2 года) плюс капецитабин в течение 6 курсов. Анализ исследования продемонстрировал сходные результаты между группами лечения через 3 года, а также не выявил никакой разницы в ОВ [28]. Более того, как в исследованиях CALGB 49907, так и в исследовании ICE у пациентов, получавших капецитабин, чаще отмечался токсический эффект, а переносимость была меньше ожидаемой.…”

Adjuvant Systemic Therapy in Older Breast Cancer Women: Can We Optimize the Level of Care?

“…Results showed no difference between the two treatment arms for the primary endpoint of three-year invasive DFS: 85.4% in women treated with capecitabine plus ibandronate vs. 84.3% in the ibandronate-alone arm; the five-year invasive DFS was 78.8% vs. 75%, respectively. Similarly, there was no difference in OS at the end of three years (95% vs. 94%) and five years (90% vs. 88%) [ 31 ]. The negative results of ICE study did not favor the use of capecitabine monotherapy, thus complementing the results of CALGB 49907 in supporting the use of combination chemotherapy as a standard adjuvant treatment for elderly women over that of capecitabine alone.…”