Abstract P1-14-01: Adding capecitabine and trastuzumab to neoadjuvant breast cancer chemotherapy - first survival analysis of the GBG/AGO intergroup-study GeparQuattro.
Authors: G von Minckwitz, M Rezai, S Loibl, PA Fasching, J Huober, H Tesch, I Bauerfeind, J Hilfrich, H Eidtmann, B Gerber, C Hanusch, J-U Blohmer, S-D Costa, C Jackisch, S Paepke, A Schneeweiss, S Kuemmel, C Denkert, K Mehta, M Untch
Journal: Cancer Research (2012)

Abstract Background: Previous results of the GeparQuattro study demonstrated that adding capecitabine either simultaneously or sequentially to EC-Docetaxel (D) neoadjuvant chemotherapy could not increase pathological complete response rates (pCR) (von Minckwitz G, JCO 2010). However, patients with HER2-positive disease treated simultaneously with trastuzumab showed a significant higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone (Untch M, JCO 2010). We here report survival after a median follow up of 58 months including 279 relapses and 191 deaths. Patients and methods: Patients with either large operable (cT3) and locally advanced (cT4) tumors, or hormone-receptor (HR)-negative receptor status, or HR-positive tumors but clinically node-positive disease were recruited to receive 4 cycles of EC (90mg/m2/600mg/m2) and randomized to either 4 cycles of D (100mg/m2) or 4 cycles of DX (75mg/m2/1800mg/m2) or 4 cycles of D (75mg/m2) followed by 4 cycles of X (1800mg/m2) (D→X). Patients with HER-2 positive tumors received 1 year of trastuzumab, the first part concurrent to all chemotherapy cycles. All patients with HR+ tumors received endocrine therapy according to current standard. The intent-to-treat survival analysis included 1421 patients for the chemotherapy question and 1495 patients for the trastuzumab question. Analyses were adjusted by age, stage, size, nodal status, histologic type, grade, hormone-receptor (HR) and HER2-status at baseline (if applicable). Results: No difference in DFS and OS was seen for patients receiving D, DX or D-X overall (hazard ratio 0.978, p = 0.984 and hazard ratio 0.986, p = 0.684, respectively) as well as by phenotype defined according to St. Gallen (all P&amp;gt;0.354). Patients with HER2-positive disease treated additionally with trastuzumab showed significantly better OS (p = 0.015) compared to patients with HER2-negative disease treated with chemotherapy alone. DFS was significantly better for trastuzumab-treated patients with HR-negative tumors (p = 0.046), but not with HR-positive tumors (p = 0.790). OS after first relapse was significantly better in trastuzumab-retreated patients with HER2-positive tumors (p = 0.032) compared to relapsed patients with HER2-negative tumors. Patients with an early response after 4 cycles, with a clinical response at surgery and with a pCR showed a significantly better DFS and OS compared to patients without pCR (p = 0.022, P &amp;lt; 0.0001, P &amp;lt; 0.0001). This benefit was most prominent in patients with triple-negative tumors. Conclusions: Survival analysis of the GeparQuattro study confirmed the results of the primary endpoint analysis on pCR. Capecitabine could not improve outcome when added to anthracycline-taxane-based chemotherapy. As suggested by a recent integrated multi-level meta-analysis (von Minckwitz, BCRT 2011) effect of capecitabine could not be properly assessed in this study as planned docetaxel doses in arms DX and D®X were lower than in arm D. Survival of HER-2 positive patients surmounts that of HER2-negative patients if trastuzumab is used in the neoadjuvant as well as in the metastatic setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-01.