Abstract OT3-3-11: A RANDOMIZED PHASE III TRIAL COMPARING NANOPARTICLE-BASED PACLITAXEL WITH SOLVENT-BASED PACLITAXEL AS PART OF NEOADJUVANT CHEMOTHERAPY FOR PATIENTS WITH EARLY BREAST CANCER (GeparSepto) GBG 69

Abstract

Abstract Background: Anthracycline/taxane based regimen are standard of care for neoadjuvant therapy in breast cancer. Recent data from the neo-Tango study suggest that a reverse sequence of taxane followed by the anthracycline can achieve higher pCR rates. Solvent-based taxanes (paclitaxel, docetaxel) cause severe toxicities most likely by the solvents such as cremophor. Nab-paclitaxel is a solvent-free formulation of paclitaxel encapsulated in albumin. It is believed that nab-Paclitaxel compared to solvent based paclitaxel followed by conventional dosed EC might further improve the pCR rate in breast cancer patients receiving neoadjuvant treatment. Previous studies have shown that dual anti-HER blockade is superior to trastuzumab alone resulting in an increase of pCR rate by 20%. Patients and Methods: The GeparSepto trial, a neoadjuvant, randomized phase III study, planned to include 1200 pts, randomized to nab-paclitaxel versus conventional, solvent based paclitaxel given weekly for 12 weeks followed in both arms by 4 cylces conventionally dosed EC. The primary objective is to compare the rate of pCR (ypT0 + ypN0). Further objectives are to compare the pCR rate in predefined subgroups, pCR by other definition, the clinical response rate and the rate of breast conserving surgery after chemotherapy in the two different treatment arms. Women with untreated, histologically confirmed uni- or bilateral, cT2- cT4d carcinoma, and no clinically relevant cardiovascular and other co-morbidities are randomized to receive either paclitaxel (80mg/m2) or nab-paclitaxel (150 mg/ m2) day 1, 8, 15, q d 22 for 4 cycles followed by conventional EC (E (90mg/m2)+C (600 mg/m2)) on day 1 q day 22 for 4 cycles. HER2 positive pts receive trastuzumab (loading dose 8mg/kg followed by 6 mg/kg) and pertuzumab (loading dose 840 mg followed by 420 mg) q3w concomitantly to the chemotherapy. Biomaterial including FFPE form core biopsy, serum, plasma, full blood is collected before randomization, after the 12 cycles for (nab−) paclitaxel therapy and after the 4 cycles of EC before surgery. The HER2, estrogen receptor, progesterone receptor, Ki67 and SPARC status will be centrally tested by immunohistochemistry prior to randomization for stratification. A broad translational program is planned. It has been assumed that solvent based taxane will achieve an overall pCR rate of 33% to be increased using nab-paclitaxel to 41%, corresponding to an odds ratio of 1.41. If 596 patients are enrolled into each arm, a χ2-test will have an 80% power with a 2-sided significance level α=0.05 to show the superiority of nab-paclitaxel. Closed test procedure will be used to test for non-inferiority of nab-paclitaxel first. The trial is registered under NCT01583426. It is financially supported by Roche and Celgene. Results: The centres have been initiated after approval by ethics committee and authorities. First patient in will be this months. It is planned to recruit 18 months in 100 sites in Germany. Conclusion: Geparsepto will investigate the efficacy of neoadjuvant nab-paclitaxel compared to solvent based paclitaxel given weekly and the dual blockade with Trastuzumab and Pertuzumab in HER 2 positive BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-3-11.