Comparison of chemotherapeutic combination therapy, dosing frequency and dosing sequence for the adjuvant treatment of early-stage breast cancer: a network meta-analysis.

[BACKGROUND] Despite the availability of several chemotherapeutic regimens for early-stage breast cancer (BC), the ideal combination and dosing strategy remain to be defined. Thus, we conducted a network meta-analysis (NMA) comparing the current chemotherapeutic regimens used in the treatment of women with early-stage BC.

[METHODS] We searched public database from inception to May 2021 for Phase II and Phase III trials of adjuvant chemotherapy in patients with early-stage BC following PRISMA guidelines. The primary end-points were event-free survival (EFS) and overall survival (OS) determined by estimates of hazard ratios (HR) and surface under the cumulative ranking curve (SUCRA) values. The safety analysis had only Grade ≥ 3 adverse effects (AEs).

[RESULTS] This NMA evaluated a total of 17,187 patients from 36 randomized controlled trials. The follow-up ranged from 22 months to 152 months (median: 12.8 years). The chemotherapeutic regimen AQ (6 T CD + C CD) had the highest SUCRA value (AQ: 0.95). Among the chemotherapeutic regimens, the AF regimen consisting of 4 A CD→T CD showed the highest probability (SUCRA: 0.92) for being the most effective treatment based on the OS. The rank probability assessment revealed that AQD contributed to the lowest incidence of nausea (SUCRA: 0.96), and C (3 CAX CD→TX CD; SUCRA: 0.79) was least likely to induce neutropenia.

[CONCLUSION] This meta-analysis confirmed that concurrent six-cycle treatment with taxane and cyclophosphamide at three-week intervals might be the optimal therapy for treating early-stage BC in the adjuvant setting.