Does the Sequence of Anthracycline and Taxane Matter? The NeoSAMBA Trial

Abstract

Background. Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely because of their later

introduction into clinical practice. However, there is no biolog- ical rationale that justifies this current standard of care. We

compared a taxane followed by an anthracycline-based regi- men with the reverse sequence in the neoadjuvant setting.

Patients and Methods. In a randomized, open-label, single- center phase II trial, women with inoperable, locally advanced,

HER2-negative breast cancer were stratified by hormone recep- tor status and randomized to three cycles of docetaxel

(T) followed by three cycles of fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus three cycles of FAC followed by three cycles of docetaxel. Surgery, radiotherapy, and adjuvant hormonal therapy were administered as per local guidelines. The primary endpoint was pathological complete response (pCR), and secondary endpoints included toxicity, event-free survival (EFS), and overall survival (OS).

Results. Treatment sequence did not improve pCR, which was 7% with T-FAC and 3% with FAC-T. However, after a median follow-up of 79 months, the 5-year EFS rate was

75.7% (95% confidence interval [CI], 65.4%–87.7%) with T- FAC and 48.2% (95% CI, 37.0%–62.7%) with FAC-T (hazard

ratio [HR], 0.46; 95% CI, 0.26–0.81; log-rank p = .0054), and the 5-year OS rate was 89.7% (95% CI, 82.2%–97.8%) with T-FAC and 64.7% (95% CI, 53.6%–78.1%) with FAC-T (HR,

0.41; 95% CI, 0.22–0.78; p = .0052). There were no unex- pected toxicities.

Conclusion. We showed for the first time an improvement in EFS and OS with taxane-first compared with anthracycline-first sequencing chemotherapy in HER2-negative, locally advanced

breast cancer. Confirmation of these results may have implica- tions for clinical practice.