Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial

• Published in: Breast cancer research and treatment 2017-02, Vol.161 (3), p.473-482
• Main Authors: Yamamoto, Daigo, Sato, Nobuaki, Rai, Yoshiaki, Yamamoto, Yutaka, Saito, Mitsue, Iwata, Hiroji, Masuda, Norikazu, Oura, Shoji, Watanabe, Junichiro, Hattori, Satoshi, Matsuura, Yoshimasa, Kuroi, Katsumasa
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anthracyclines; Anthracyclines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer metastasis; Cancer research; Cancer therapies; Capecitabine - administration & dosage; Care and treatment; Clinical Trial; Clinical trials; Comparative analysis; Dosage and administration; Drug therapy; Female; Humans; Medicine; Medicine & Public Health; Metastasis; Middle Aged; Neoplasm Staging; Oncology; Product development; Quality of Life; Retreatment; Survival Analysis; Taxoids - administration & dosage; Taxoids - therapeutic use; Treatment Outcome
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-016-4075-6

Purpose The randomized phase III JO21095 trial compared the efficacy and safety of low-dose capecitabine plus docetaxel combination therapy (XT) versus single-agent administration of docetaxel in anthracycline-pretreated HER2-negative metastatic breast cancer. Methods Patients were randomized to either low-dose XT (capecitabine 825 mg/m 2 twice daily, days 1–14; docetaxel 60 mg/m 2 , day 1 every 3 weeks) or docetaxel (70 mg/m 2 , day 1 every 3 weeks). The primary objective was to demonstrate superior progression-free survival (PFS) with low-dose XT versus single-agent docetaxel. Overall survival (OS) and safety were secondary endpoints. Results In total, 162 patients were treated. Median PFS was 10.5 months with low-dose XT and 9.8 months with single-agent docetaxel (hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.40–0.97]; p  = 0.03). The OS HR was 0.89 (95% CI 0.52–1.53; p  = 0.68). Grade ≥3 treatment-related toxicities occurred in 74% of XT-treated patients and 76% of docetaxel-treated patients. The main differences in grade ≥3 treatment-related toxicities were hand-foot syndrome (7.3% of XT-treated patients vs 0% receiving docetaxel), fatigue/malaise (2.4 vs 10.0%), and peripheral edema (1.2 vs 7.5%). Dose modifications were required in 100% of low-dose XT and 49% of docetaxel patients. Toxicity-related treatment discontinuations occurred in 18 and 33%, respectively. Conclusion The improved PFS with low-dose XT versus docetaxel alone is consistent with higher-dose XT phase III experience, but the safety profile was more favorable and manageable.