Taxanes (T) plus bevacizumab (B) and taxanes plus capecitabine (X) showed better progression-free survival (PFS) compared to taxanes alone. Since life-threatening or highly symptomatic situations require polychemotherapy in metastatic breast cancer (MBC), combination of taxanes, capecitabine plus bevacizumab appears reasonable. TABEA (NCT01200212), a prospectively randomized, open-label, phase III trial compares taxanes (paclitaxel 80 mg/m(2) i.v. d1,8,15 q22 or docetaxel 75 mg/m(2) i.v. d1 q22) plus bevacizumab (15 mg/kg i.v. d1 q22) with (TBX) or without capecitabine (TB, 1800 mg/m(2) daily d1-14 q22) as first-line therapy in MBC. Histologically confirmed HER2-negative, locally advanced or MBC patients with a chemotherapy indication and measurable or non-measurable target lesions (RECIST criteria) were included. Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (complete response, partial response, stable disease ≥24 weeks), 3-year overall survival, PFS in patients ≥65 years, toxicity, and compliance. We assumed 10 and 13.3 months PFS for TB and TBX, respectively (HR = 0.75), requiring 432 patients and 386 events. Preplanned interim futility and safety analyses after 100 events in 202 patients showed no efficacy benefit and higher toxicity for TBX. Recruitment and therapy were stopped following advice from the IDMC. Final analysis revealed a HR 1.13 [95 %CI 0.806-1.59], P = 0.474, for PFS. Overall grade 3-4 adverse event (77.3 vs. 62.1 %, P = 0.014) and serious adverse event (40.0 vs. 30.2 %, P = 0.127) rates were higher for TBX after 26.1 months median follow-up, with six deaths for TBX versus 1 for TB. Adding capecitabine to TB cannot be recommended as first-line therapy in MBC.
TPS1141 Background: Anthracyclines (A) followed by taxanes (T) are standard of care for neoadjuvant therapy in breast cancer (BC). A reverse sequence of T followed by A was suggested to achieve higher pCR rates. Previous studies have shown that dual anti-HER2 blockade is superior to trastuzumab (H) alone and thus can increase the pCR rate by 20%. Nab-paclitaxel (nP) is a solvent-free formulation of P encapsulated in albumin and might also improve the pCR rate with eventually lower toxicity. Methods: The GeparSepto study (NCT01583426) will randomize 1200 patients to either nP (150 mg/m²) q1w or P (80mg/m²) q1w for 12 weeks followed by 4 cycles conventionally dosed EC (E 90mg/m², C 600 mg/m²) q3w for 4 cycles. Primary objective is to compare the pCR rate (ypT0+ ypN0). Patients with untreated, histologically confirmed cT2- cT4d BC can be included. HER2+ patients receive H (loading dose 8mg/kg; 6 mg/kg) plus pertuzumab (loading dose 840 mg; 420 mg) q3w concomitantly. Biomaterial including FFPE from core biopsy, serum, plasma and full blood is collected. HER2, ER, PgR, Ki67 and SPARC status will be centrally assessed prior to randomization for stratification. P was assumed to achieve a pCR rate of 33% which will be increased to 41% when using nP, corresponding to an odds ratio of 1.41. To investigate resistance to anti-HER2 treatment, patients with HER2+ BC are randomized prior to start of chemotherapy to receive either 6 weeks H, pertuzumab or the combination as biological window with biomaterial collection prior to start of therapy and after week 6 prior to start of chemotherapy. Results: After been approved by ethics committees and authorities recruitment started in 7/2012 in 56 sites. 293 patients were recruited (53 HER2+; 240 HER2-) by 1st Feb 2013. A first safety interim analysis is planned after 60 patients have finished therapy. Conclusions: GeparSepto investigates the efficacy of neoadjuvant nP compared to solvent-based P given weekly with a dual blockade of the HER2 receptor in HER2-pos BC. Interim safety results for nP will be presented. The window-substudy is funded within the EU-FP7 project RESPONSIFY No 278659. Clinical trial information: NCT01583426.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.