Abstract PD07-06: NEO-ZOTAC: Toxicity data of a phase III randomized trial with NEOadjuvant chemotherapy (TAC) with or without ZOledronic acid (ZA) for patients with HER2-negative large resectable or locally advanced breast cancer (BC)

Abstract

Abstract Background: The role of bisphosphonates (BP) when added to the (neo)adjuvant treatment of BC in enhancing the efficacy of therapy is still unknown. NEOZOTAC investigates the efficacy of ZA added to neoadjuvant chemotherapy in patients with HER2-negative BC. Trial design: NEOZOTAC is a Dutch multicenter study. Patients are 1:1 randomized to 3-weekly TAC (docetaxel 75mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2 i.v., day 1) chemotherapy supported by pegfilgrastim (6 mg sc), day 2 with or without ZA (4 mg i.v. within 24 hr after chemotherapy) q3 weeks. Eligibility criteria: Main inclusion criteria: stage II or III, measurable, HER2-negative BC, age ≥18 years, WHO 0–2, adequate bone marrow-, renal-, and liver function, absence of prior BP usage and absence of active dental problems. Study endpoint: The primary endpoint is the pathologic complete response (pCR) rate. Secondary endpoints are toxicity, clinical response, tumor heterogeneity in core biopsy vs. operation specimen, and (disease free) survival. Optional side studies include fluorescent imaging (SoftScan®), changes in bone markers, single nucleotide polymorphisms and the insulin-like growth factor pathway, circulating tumor and endothelial cells and the false-negative rate of the sentinel node biopsy after neoadjuvant chemotherapy. Statistical Methods: Using a 5% significance level based on the two-sided Fishers exact test with a power of 80%, 250 patients (125/arm) are needed to show an improvement of the pCR-rate from 17% to 34% in the experimental arm. Randomization was done according to the Pococks minimisation technique stratified by cT, cN, and estrogen receptor status. Toxicity is analyzed using the Exact (2-sided) Chi-Square test. Results: From July 2010 to April 2012, 250 patients from 25 participating sites were randomized. Toxicity data of 173 patients are currently available and data of all 250 patients will be presented at SABCS. Patient characteristics are presented in table 1. Hematological and non-hematological toxicities were not significantly different between both treatment arms. Main grade 3/4 NCI-CTCv4 toxicities were neutropenia (8%), followed by febrile neutropenia (7%), fatigue (6%), diarrhea, hypertension, nausea (3%) and vomiting (1.2%). Bone pain, myalgia, and hypocalcemia occurred in one patient in the TAC-ZA arm (0.6%). Osteonecrosis of the jaw was not observed. Conclusions: Neoadjuvant TAC supported by pegfilgrastim plus ZA is feasible. No significant difference in toxicity are reported compared with the control arm. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-06.