Medical Oncology, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Clinical Research, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Oncologist. 2020 Sep;25(9):758-764. doi: 10.1634/theoncologist.2019-0805. Epub 2020 Jun 23.
Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely because of their later introduction into clinical practice. However, there is no biological rationale that justifies this current standard of care. We compared a taxane followed by an anthracycline-based regimen with the reverse sequence in the neoadjuvant setting.
In a randomized, open-label, single-center phase II trial, women with inoperable, locally advanced, HER2-negative breast cancer were stratified by hormone receptor 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).
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 unexpected toxicities.
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 implications for clinical practice. This trial was registered with Clinicatrials.gov identifier NCT01270373.
The NeoSAMBA trial showed a benefit for taxane-first sequencing chemotherapy consistent with the systematic review of the literature as well as the larger Neo-tAnGo study. Many recent and current ongoing clinical trials have already followed this treatment strategy. As a taxane-before-anthracycline sequence carries neither an incremental cost nor an increased toxicity, and given the available literature on this issue, reinforced that taxane-first regimen can be easily incorporated into daily clinical practice while awaiting confirmation of these findings from larger trials.
紫杉烷类药物通常在乳腺癌新辅助/辅助治疗中紧随蒽环类药物之后，可能是因为它们后来才被引入临床实践。然而，目前这种护理标准并没有生物学上的理由。我们比较了紫杉烷类药物加蒽环类药物序贯治疗与反序治疗在新辅助治疗中的效果。
在一项随机、开放标签、单中心的 II 期试验中，将无法手术的局部晚期、HER2 阴性乳腺癌患者按激素受体状态分层，并随机分为三组：三组接受多西紫杉醇（T）加氟尿嘧啶、多柔比星和环磷酰胺（FAC），共 3 个周期，然后再接受 3 个周期的多西紫杉醇；三组先接受 FAC，共 3 个周期，然后再接受 3 个周期的多西紫杉醇。手术、放疗和辅助激素治疗均按照当地指南进行。主要终点是病理完全缓解（pCR），次要终点包括毒性、无事件生存（EFS）和总生存（OS）。
治疗顺序并没有提高 pCR，T-FAC 组为 7%，FAC-T 组为 3%。然而，中位随访 79 个月后，T-FAC 组的 5 年 EFS 率为 75.7%（95%置信区间[CI]，65.4%-87.7%），FAC-T 组为 48.2%（95% CI，37.0%-62.7%）（风险比[HR]，0.46；95% CI，0.26-0.81；对数秩检验 p =.0054），T-FAC 组的 5 年 OS 率为 89.7%（95% CI，82.2%-97.8%），FAC-T 组为 64.7%（95% CI，53.6%-78.1%）（HR，0.41；95% CI，0.22-0.78；p =.0052）。没有出现意外毒性。
我们首次表明，在 HER2 阴性、局部晚期乳腺癌中，与蒽环类药物序贯化疗相比，紫杉烷类药物序贯化疗可提高 EFS 和 OS。这些结果的证实可能对临床实践有影响。这项试验在 Clinicatrials.gov 注册号为 NCT01270373。
NeoSAMBA 试验显示，与文献系统评价以及更大的 Neo-tAnGo 研究一致，紫杉烷类药物序贯化疗具有获益。许多最近和正在进行的临床试验已经遵循了这种治疗策略。由于紫杉烷类药物加蒽环类药物序贯治疗既没有增加成本，也没有增加毒性，而且鉴于这方面的文献，在更大规模的试验证实这些结果之前，这种紫杉烷类药物优先的治疗方案可以很容易地纳入日常临床实践。
