Ixabepilone plus capecitabine improves progression free survival in patients with metastatic breast cancer resistant to taxanes: a pooled analysis from two phase III trials.

Abstract

Abstract Abstract #2015 Background:
 Patients (pts) with MBC whose tumors are resistant to taxanes (T) have limited therapeutic options. Ixabepilone (ixa), the first in a new class of antineoplastic agents, showed clinical benefit in combination with capecitabine (C) in 2 large clinical trials in metastatic breast cancer (MBC) pts resistant to (study 046, JCO, 2007), or pretreated with anthracycline (A) and T (study 048). Pts whose tumors were resistant to A/T were also allowed to enter the 048 trial. In 048, ixa + C, compared to C alone, also demonstrated significant increases in progression-free survival (PFS, HR 0.79 [0.69-0.90)]) and ORR (43% vs 29%). A trend toward increased OS was seen both in 048 (HR 0.90 [0.78-1.03]) and in 046 (HR 0.90 [0.77-1.05]), which did not reach statistical significance. Here we present a pooled analysis from the 2 studies of clinical outcomes (ORR, PFS, and OS) in patients with a strict definition of resistance to T.
 Methods:
 1973 pts with MBC previously treated with an A and T, were randomized in phase III trials to receive either ixa (40 mg/m2 IV over 3h Q3w) + C (1000 mg/m2 PO BID x14d Q3w) or C alone (1250 mg/m2 PO BID x14d Q3w). For both studies, resistance was defined as disease progression up to 4 months following T in the metastatic setting and up to 12 months following adjuvant T therapy. Due to the similarity of the study populations, individual pt data from both studies was pooled to better evaluate treatment effect within pre-planned patient subgroups.
 Results:
 1337 pts from the 2 studies were T resistant and randomized to ixa + C or C alone. ORR and PFS favored ixa + C in this pt population, and there was a trend towards increased OS, which did not reach statistical significance (see table).
 
 Conclusion:
 Ixa + C is the first combination to show a clinical benefit of PFS in pts with MBC resistant to T (following a strict definition of resistance). The benefit seen in this pooled analysis was consistent with that observed in the resistant pt population from the individual studies as well. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2015.