OT3-01-04: TANIA: A Randomized Phase III Trial Evaluating Continued and Reintroduced Bevacizumab (BEV) in Patients Previously Treated with 1st-Line BEV for Locally Recurrent/Metastatic Breast Cancer (LR/mBC).
Authors: Minckwitz G von, J Cortés, J Gligorov, NW Marschner, F Puglisi, E Vrdoljak, A-A Duenne, C Zielinski
Journal: Cancer Research (2011)

Abstract Background BEV has repeatedly demonstrated improvements in progression-free survival (PFS) in randomized phase III trials, providing benefit in the 1st- and 2nd-line settings when combined with chemotherapy versus chemotherapy alone. However, the role of BEV in BEV-pretreated LR/mBC is unclear. The TANIA trial (MO22998) was initiated to address this question. Trial design: TANIA is an open-label randomized multicenter phase III trial. Eligible patients are aged ≥18 years with HER2−negative LR/mBC that has progressed during or after ≥12 weeks of 1st-line BEV combined with chemotherapy for LR/mBC. Maintenance therapy with BEV and/or endocrine therapy before study enrollment is permitted. Patients who have previously received anti-angiogenic therapy other than BEV in the 1st-line LR/mBC setting are not eligible. BEV-specific exclusion criteria are similar to previous randomized trials (eg inadequately controlled hypertension; history of nephrotic syndrome, hypertensive crisis, gastrointestinal perforation, or grade 3/4 venous thromboembolism; significant vascular disease). All patients must provide written informed consent. After stratification according to hormone receptor status, time to 1st progression (&amp;lt;6 vs ≥6 months), choice of chemotherapy (taxane vs non-taxane vs vinorelbine), and LDH level (≤1.5 vs &amp;gt;1.5 * upper normal limit), eligible patients are randomized 1:1 to 2nd-line treatment with either standard single-agent chemotherapy alone (arm 1) or standard single-agent chemotherapy combined with BEV (15 mg/kg q3w or 10 mg/kg q2w, depending on the chosen chemotherapy regimen; arm 2). 2nd-line therapy is continued until disease progression, unacceptable toxicity, or patient withdrawal. At progression, patients in arm 1 receive 3rd-line chemotherapy without BEV (ie no crossover permitted) and those in arm 2 receive 3rd-line chemotherapy in combination with BEV (unless prevented by unacceptable toxicity). Maintenance endocrine therapy is permitted in both arms (in combination with BEV in arm 2). At 3rd progression, BEV is permitted in all patients. The primary objective is to determine the therapeutic benefit of continued or reintroduced BEV in combination with 2nd-line chemotherapy for patients previously treated with 1st-line BEV plus chemotherapy, determined by the duration of PFS from the time of randomization to 2nd progression (or death). Additional objectives include evaluation of the interval between 2nd and 3rd progression, the interval between randomization and 3rd progression, PFS in stratified subgroups, overall response rate to 2nd-line therapy, overall survival (OS), 1-year OS rate, safety, quality of life (FACT-B and EQ-5D), and translational research. The sample size of 488 patients is calculated assuming median PFS of 7 months in arm 1, a hazard ratio of 0.75, a recruitment period of 30 months, and a 5% dropout rate (ie 439 eligible patients), providing 80% power at two-sided a=0.05. As of 15th June 2011, 23 patients have been enrolled. The primary analysis is planned after 384 patients have shown progression on 2nd-line therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-04.