A dose-escalating study of XRP6258 in combination with capecitabine, in patients (pts) with metastatic breast cancer (MBC) progressing after anthracycline and taxane therapy: Preliminary results

Abstract

1053 Background: Cabazitaxel (X), a new taxoid showed activity in taxane resistant MBC. Capecitabine (C) is approved in MBC pts pretreated with anthracycline and taxane. Methods: A standard 3+3 escalation scheme explored doses of combined intravenous X (Day (D)1) with oral C twice daily (D1to14), every 3 weeks (q3w). The study objectives were the identification of dose limiting toxicities (DLTs), recommended dose (RD) of the combination, assessment of safety, pharmacokinetics (PK) and activity at the RD in an expanded cohort. Results: 32 MBC pts pretreated with taxane and anthracycline were enrolled and treated (15 in the dose escalation part and 17 at the RD). Data for the first 25 pts, are available so far: median age 52 [34–74], ECOG-PS 0/1: 15/10, in first or second line chemotherapy, median of 3 (1–7) organs involved (mainly: bone, liver, lymph nodes). In the escalation part, X+C were administered at 3 dose levels (DL) (Table). DL2 was defined as the RD and the expansion cohort was initiated. PK analysis did not show any drug-drug interaction with this schedule of administration. Overall, out of the 25 pts (125cy), the main Gr3–4 toxicities (N pts) were asthenia (4), hand-foot syndrome (4), neutropenia (15), febrile neutropenia (1), neutropenic infection (1), no toxic death. Efficacy was observed at each DL with a total of 1 complete response, 4 partial responses (PR) and 16 stabilizations (including 3 unconfirmed PR). Conclusions: X was safely combined to C. X at 20 mg/m2 D1 + C at 1000 mg/m2 twice a D (D1–14), q3w is the RD. Updated results for efficacy and safety will be presented. [Table: see text] [Table: see text]