Pooled analysis of individual patient data from capecitabine monotherapy clinical trials in locally advanced or metastatic breast cancer.

We assessed the efficacy and safety of capecitabine across treatment lines, and the impact of patient and disease characteristics on outcomes using data from phase II/III trials. Individual patient data were pooled from seven Roche/Genentech-led trials conducted from 1996 to 2008 where single-agent capecitabine was the test or control regimen for metastatic breast cancer (MBC). Data were analyzed from 805 patients: 268 in the first-line metastatic setting and 537 in the second-line or later setting. Baseline characteristics were balanced across treatment lines. Patients receiving second-line or later versus first-line capecitabine had lower objective response rates (ORR: 19.0 vs. 25.0 %, respectively, odds ratio 0.70; 95 % CI: 0.5-1.0) and significantly shorter progression-free survival (PFS: median 112.0 days [3.7 months] vs. 150.0 days [4.9 months]; p < 0.0001) and overall survival (OS: median 396.0 days [13.0 months] vs. 666.0 days [21.9 months]; p < 0.0001). In multivariate analysis by backward elimination, significantly improved ORR (p = 0.0036), PFS (p < 0.0001) and OS (p < 0.0001) with capecitabine were demonstrated in patients with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive versus both ER and PgR-negative tumors. Hand-foot syndrome (HFS) was the most common adverse event (AE) in 63 % of patients. Overall, 7 % of patients discontinued and two patients (<1 %) died from treatment-related AEs. Significantly improved survival was observed in patients developing capecitabine-related HFS (p < 0.0001 PFS/OS) or diarrhea (p = 0.004 OS; p = 0.0045 PFS) versus patients without these events. In this pooled analysis of individual patient data, first-line capecitabine was associated with improved ORR, PFS, and OS versus second or later lines. Multivariate analyses identified greater ORR, PFS, and OS with capecitabine in patients with ER and/or PgR-positive versus ER/PgR-negative tumors. Safety was in-line with previous phase III trials in MBC.