Background: We previously showed that intense dose-dense (idd) epirubicin (E), paclitaxel (T), cyclophosphamide (C) results in a superior DFS and OS compared to conventionally dosed EC-T in pts with primary breast cancer (PBC) and ≥4 involved lymph nodes (LN) (Möbus et al JCO 2010). In the GAIN study, the intense dose-dense strategy has been further investigated as well as the adjuvant application of ibandronate (I). We here report on the planned interim efficacy analysis after 50% (N>401) of the required events have occurred. Methods: A prospective, multi-center, controlled, non-blinded, randomized phase III trial investigating ETC (E: 150 mg/m2, T:225 mg/m2, C:2500–2000 mg/m2, i.v. day 1, q15 for 3 cycles each: A1); or EC→TX (E: 112.5 mg/m2 + C: 600 mg/m2, i.v. day 1, q 15 for 4 cycles→T: 67.5 mg/m2 i.v. day 1, q 8 for 10 weeks + X: 2000 mg/m2 p. o. day 1–14, q 22 for 4 cycles: A2). Pts were further randomized in a 2:1 ratio to receive ibandronate: 50 mg/day p.o. for 2 years (B1) or observation (B2). Pts received a primary prophylaxis with either epoetin β or darbepoetin α and pegfilgrastim during ETC or EC. After recruitment of 1500 pts prophylactic ciprofloxacin was implemented and the dose of C was reduced to 2000 mg/m2. Eligibility: Females ≥18 and <65 years, histologically confirmed LN positive uni- or bilateral PBC; adequate surgery, ≥1 pos.LN; ECOG ≤2; written informed consent. Primary objective:compare DFS A1 vs. A2 and B1 vs.B2. Secondary objectives: OS, safety, incidence of secondary primaries, and EFS in subgroups of hormone sensitivity and number of pos. LN between arms; assessment of compliance; determine prognostic factors. 3000 pts with 801 events were needed to show an increase of 5-year DFS from 75% to 79% for pts receiving EC→TX and 728 events to show an increase of 5-year DFS from 75% to 79.5% for pts receiving I, assuming a drop-out rate of 5%, α=0.05 (two-sided)and 1-β =80%. An interim analysis for both primary objectives was planned after 50% of the expected events occurred. Safety results have been reported previously (Möbus et al. SABCS 2009). Results: 3023 patients were randomized between 06/2004 and 08/2008.1512 received ETC and 1511 EC→TX. 29pts never started therapy, 14 in ETC, 15 in EC→TX. Median follow-up is 38.7 months. Median age was 50 years; pN1 (37.7%), pN2 (35.4%); pN3 (26.9%); 77.4% had ductal invasive carcinoma, 46.6% were grade 3; 76.7% had hormone receptor-positive tumors, 22% were HER2−positive. 405 events have occurred by 12.05.2011.380pts relapsed and 25pts. died w/o relapse. The interim futility boundary for chemotherapy was not crossed. For the ibandronate question the futility boundary was reached. There was no difference in DFS and OS between the patients with and without ibandronate (DFS log-rank p=0.593; HR 1.059; 95%CI 0.861−1.301; OS log-rank p=0.801 HR 0.961; 95% CI 0.705−1.31). Conclusion: The GAIN study demonstrated that adjuvant ibandronate does neither improve DFS nor OS in primary node positive breast cancer after treatment with dose-intensified chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S2-4.
Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with reduced clinical outcome. Bisphosphonate treatment was shown to eradicate DTC from BM in several studies. This controlled randomized open-label multi-center study aimed to investigate the influence of zoledronic acid (ZOL) on DTC and survival of breast cancer patients (Clinical Trial Registration Number: NCT00172068).
BACKGROUND RESULTS Breast cancer is the most common malignant disease in women in Western countries and is still the leading cause of cancer death in women. About 5% of women with breast cancer have distant metastatic disease at initial presentation. Furthermore, 25% of patients with early-stage disease treated with post-operative adjuvant therapy experience a recurrence, peaking 2 years after initial diagnosis. Metastatic breast cancer is a highly heterogeneous disease that has a vast variety of clinical scenarios, ranging from solitary metastatic lesions to diffuse, multiple organ involvement and thus, varying prognostic outcomes. The last two decades have seen the introduction of a variety of new chemotherapeutic agents, endocrine agents and biological agents leading to a positive impact on the survival of women with metastatic breast cancer. Breast Cancer registries can help to understand how patients are treated outside clinical trials and what outcome is to be expected for specific patient groups and therapy lines, which are not included into clinical trials. The aim of the current analysis was to determine outcome in different metastatic breast cancer scenarios. For this purpose we analyzed overall survival data according to therapy line, breast cancer subtype, metastatic site and performance status. The PRAEGNANT study is conducted as a prospective diagnostic translational and multi-centric registry with a central documentation of patient and tumor characteristics and a central biomaterial archive for prospective molecular analyses. The Study network aims at registering 3500 breast cancer patients with advanced, incurable, metastatic disease. Patients of all therapy lines with any kind of treatment are eligible for this registry. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Data collection Clinical data were collected by trained and dedicated staff at the sites participating in the prospective PRAEGNANT study. These data are monitored using automated plausibility checks and through random on-site field monitoring. Statistical methods Overall survival rates according to subtype, metastatic site, performance status and primary metastatic disease were estimated in patients that were treated in the 1 st line metastatic situation using the Kaplan-Meier product limit method. Overall survival analyses according to therapy line was performed in the whole data set. Survival curves were compared using log-rank tests.
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