Abstract P1-12-01: Evaluation on efficacy and safety of capecitabine plus docetaxel versus docetaxel monotherapy in metastatic breast cancer patients pretreated with anthracycline: Results from a randomized phase III study (JO21095)
Authors: Sato N , Yamamoto D , Rai Y , Iwase H , Saito M , Iwata H , Masuda N , Oura S , Watanabe J , Kuroi K 
Published: August 2014

Abstract
Introduction: A previous large-scale phase III study demonstrated that, compared with docetaxel (T) alone, capecitabine (X) and T in combination (XT) offered significantly superior progression free survival (PFS) and overall survival (OS) in metastatic breast cancer (MBC). However, XT increased Grade 3/4 adverse events (AEs) which led to more frequent dose reductions than with T alone. Optimal dose of XT in Japanese was examined in a phase Ib study. Based on the background, we conducted a phase III randomized study in Japanese HER2 negative MBC patients pre-treated with anthracycline to compare efficacy and safety of XT therapy and T therapy.
Methods: Eligible pts were HER2-negative MBC pts with anthracycline-pretreatment, a measurable tumor, and ECOG performance status of 0 or 1. Pts were randomly assigned to the XT group or the T→X group. The XT group received concurrent therapy of X (1650 mg/m2/day from day 1 to 14) and T (60 mg/m2) in 3-week cycle. The T→X group received sequential therapy of T (70 mg/m2) in 3-week cycle followed at disease progression by X (2500 mg/m2/day from day 1 to 14 followed by 1-week rest). Primary endpoint was PFS. Secondary endpoints were OS, overall response rate (ORR), time to treatment failure (TTF), safety, and quality of life. The XT group and the T phase of the T→X group (T group) were compared in our evaluation.
Results: Of 163 pts enrolled, 156 were eligible. Baseline characteristics of all pts in each group were well balanced. The median delivered dose was 79.0% and 95.1% of the planned dose respectively for X and T in the XT group, and it was 97.2% in the T group. Median PFS in the XT group was 10.5 months compared to 9.8 months in the T group (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40–0.97). The ORR was 70% and 61%; the median TTF was 9.6 months and 7.0 months in the XT group and the T group, respectively. Median OS has not been reached yet. Subgroup analysis showed PFS was longer in pts with liver metastasis (HR, 0.39; 95% CI, 0.19–0.84) and in pts with lung metastasis (HR, 0.43; 95% CI, 0.21–0.90) in the XT group. Incidence of treatment related AEs (TR-AEs) ≥Grade 3 was 74.4% (61 pts) in the XT group and 76.3% (61 pts) in the T group. Frequently reported TR-AEs ≥Grade 3 were; decrease in neutrophil count (XT, 57.3%; T, 60.0%), neutropenia (XT, 8.5%; T, 12.5%) and febrile neutropenia (XT, 6.1%; T, 10.0%). TR-AE ≥Grade 3 in the XT group with incidence at least 5% higher than the T group was hand-foot syndrome (XT, 7.3%; T, 0%). On the other hand, TR-AEs ≥Grade 3 in the T group with incidence at least 5% higher than the XT group were fatigue (XT, 2.4%; T, 8.8%) and peripheral edema (XT, 1.2%; T, 6.3%).
Conclusion: The concurrent therapy of XT demonstrated significant improvement of PFS compared with T alone. Superior efficacy of XT therapy was reported as same as the previously reported study on XT versus T although the dose was lower in our study. Considering the efficacy and tolerability, we consider concurrent Japanease dose XT therapy is a preferable treatment for MBC pts with liver or lung metastasis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-12-01.