Abstract PD01-03: Review of Capecitabine for the Treatment of Triple-Negative Early Breast Cancer

Abstract

Abstract Background: Patients with triple-negative breast cancer (TNBC) have a high unmet therapeutic need with a generally poor prognosis. Initial data from two randomised, phase III trials of capecitabine (C) in early breast cancer (EBC), ABCSG-24 and FinXX, are promising. ABCSG-24 demonstrated significant improvements in pathological complete response (pCR) rate with the incorporation of C into a neoadjuvant regimen of epirubicin (E) plus docetaxel (D) (24.3% vs 16.0%; p=0.02) [Steger G, et al. ECCO-ESMO 2009; Abst 4BA]. FinXX revealed significant improvements in 3-year recurrence-free survival (RFS) with the addition of C to a sequential taxane-anthracycline adjuvant regimen (92.5% vs 88.9% control; hazard ratio [HR] 0.66, 95% CI 0.47-0.94; p=0.020) [Joensuu H, et al. Lancet Oncol 2009]. We review subgroup analyses from these two studies in patients with TNBC to assess the potential benefit of C in this patient subgroup. Methods: Patients with operable breast cancer except T4d, ± nodal involvement were randomised in the ABCSG-24 study to 6x ED every 21 days (dl: E 75mg/m2 and D 75mg/m2, d2: pegfilgrastim 6mg) ± C (1,000mg/m2 b.i.d., d1-14). Patients with medium-to high risk EBC were randomised in the FinXX study to 3x D≥3x CycEF (D 80mg/m2 d1→cyclophosphamide [Cyc] 600mg/m2 d1, E 75mg/m2 d1, F 600mg/m2 d1, every 21 days) or 3x CD≥3x CycEC (C 900mg/m2 bid d1-15 + D 60mg/m2 d1→Cyc 600mg/m2 d1, E 75mg/m2 d1, C 900mg/m2 b.i.d., d1-15, every 21 days). Results: Patients with TNBC in the ABCSG-24 study (n=122) had a significantly greater chance of achieving a pCR than non-TNBC (n=348) (odds ratio [OR] 5.29, 95% CI: 3.22-8.68, P<0.0001), irrespective of the regimen. In the total study population, the highest pCR rates were achieved in patients with TNBC receiving EDC therapy (47.5% vs 31.2% with ED; p=NS). Patients with TNBC in the FinXX study (n=202) had significantly shorter RFS than patients without TNBC (n=1,294) (81.7% vs 92.2%, HR 0.43, 95% CI 0.29-0.63; P<0.001). Within the TNBC subgroup, 3-year RFS was significantly longer in the C-containing arm (n=93) than in the control arm (n=109) (87.7% vs 76.6%, respectively; HR 0.43, 95% CI 0.21-0.90; p=0.024). RFS did not differ significantly in the C arm among patients with TNBC or non-TNBC (HR 0.74, 95% CI: 0.38-1.41; p=0.357). Conclusions: Initial data for C in EBC are promising with the ABCSG-24 and FinXX randomised, phase III trials demonstrating significant improvements in pCR and RFS, respectively, with the addition of C to standard (neo)adjuvant regimens. Exploratory subgroup analyses from these studies show additional benefit of C therapy in patients with TNBC, who are typically recognised as a group with poorer prognosis. An ongoing randomised, phase III study conducted by the CIBOMA collaborative group is prospectively investigating C maintenance therapy after adjuvant anthracycline/taxane in patients with TNBC. This is the first study of C to specifically target patients with early TNBC and interim safety data are expected in 2010. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD01-03.