Capecitabine/trastuzumab for the first-line treatment of patients with HER2-positive metastatic breast cancer (MBC).

Abstract

1139 Background: Preclinical studies demonstrate at least additive effects on tumor growth inhibition and growth delay when trastuzumab (H) is combined with capecitabine (X) in human breast cancer xenograft models, and provide a rationale for the development of XH combination therapy in patients with HER2-positive MBC. Data from the randomized, phase III GBG-26/BIG03-05 study demonstrated that this combination is active in patients with H-pretreated MBC, with no unexpected side effects. Phase II studies have also shown the efficacy of XH therapy in anthracycline-/taxane-pretreated MBC. This review evaluates the available evidence for XH-based therapy in the first-line MBC setting. Methods: We reviewed efficacy and safety data for 335 patients who received XH combination therapy as first-line treatment for HER2-positive MBC in four phase II studies. Wardley et al. randomized patients with HER2-overexpressing, inoperable MBC to H-docetaxel (T) with or without X until disease progression (CHAT study). In another nonrandomized study women with HER2-postive MBC received XH plus oral vinorelbine (N). A further two uncontrolled, single-arm trials in China and Japan assessed XH therapy in patients with HER2-positive MBC. Results: Across studies, median overall response rates (ORR) were 63-77%, and median time to progression (TTP)/progression-free survival (PFS) was 9.2-18.6 months. Median overall survival (OS) of up to 25.6 months was reported (Table). The regimens were generally well tolerated, with manageable adverse event profiles. The most common nonhematological grade 3/4 adverse events were hand-foot syndrome (2-20%) and diarrhea (2-16%). In the CHAT and HXN studies grade 3/4 neutropenia and febrile neutropenia were seen in 54-69% and 8-15% of patients, respectively. Conclusions: These data support the consideration of XH combinations in first-line treatment of metastatic HER2-positive breast cancer. Regimen n ORR, % Median TTP, months OS, months XHT 222 70.5 18.6 Not reached XHN 50 77 12.8* Not reached XH (China) 43 63 NR NR XH (Japan) 20 65 9.2 25.6 * PFS; NR > not reported Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche