Background:Patients with endocrine-resistant metastatic breast cancer (MBC) require cytostatic therapy. Single-agent taxanes and anthracyclines, including pegylated liposomal doxorubicin (PLD), are standard treatment options. There are no prospective data regarding optimal treatment sequences, and real-world data regarding both treatment options are limited.Methods:We analyzed electronic records of all patients with Her2-negative MBC treated with either first-line PLD or first-line taxane and subsequent crossover at the University Hospital Basel between 2003 and 2021. The primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). We used the Kaplan–Meyer method and logrank test to compare time-to-event endpoints and the Fisher exact test to compare discrete variables.Results:We retrospectively identified 42 patients with Her2-negative MBC who have received either single-agent PLD or single-agent taxane as first-line chemotherapy with subsequent crossover, including 23 patients who received first-line PLD and 19 patients who received first-line taxane. Baseline characteristics were similar between treatment groups. Treatment sequence PLD–taxane was significantly inferior to taxane–PLD regarding all endpoints: median TTNC 4.9 vs. 9.9 months (p= 0.006), median OS 17.8 vs. 24.6 months (p= 0.05), median PFS 4.4 vs. 9.0 months (p= 0.005), and ORR 13% vs. 53% (p= 0.01).Conclusions:Here, we report a first retrospective head-to-head comparison of the treatment sequence PLD–taxane versus taxane–PLD in patients with MBC, showing a substantial advantage of using taxanes first, followed by PLD. An inherent treatment bias in favor of first-line taxanes cannot be excluded, thus calling for prospective validation.
背景：内分泌治疗耐药的转移性乳腺癌患者需要接受细胞抑制治疗。单药紫杉烷类和蒽环类药物（包括聚乙二醇化脂质体阿霉素）是标准治疗方案。目前尚无关于最佳治疗顺序的前瞻性数据，且两种治疗方案的真实世界数据均有限。 方法：我们分析了2003年至2021年间巴塞尔大学医院所有接受一线PLD或一线紫杉烷类治疗并后续交叉治疗的Her2阴性MBC患者的电子病历。主要终点为至下次化疗或死亡时间。次要终点包括总生存期、无进展生存期和客观缓解率。采用Kaplan-Meier法和时序检验比较时间相关终点，使用Fisher精确检验比较分类变量。 结果：回顾性分析共纳入42例接受单药PLD或单药紫杉烷类一线化疗并后续交叉治疗的Her2阴性MBC患者，其中23例接受一线PLD治疗，19例接受一线紫杉烷类治疗。两组基线特征相似。在所有终点指标上，PLD-紫杉烷治疗顺序均显著劣于紫杉烷-PLD顺序：中位TTNC为4.9个月对比9.9个月，中位OS为17.8个月对比24.6个月，中位PFS为4.4个月对比9.0个月，ORR为13%对比53%。 结论：本研究首次对MBC患者PLD-紫杉烷与紫杉烷-PLD治疗顺序进行回顾性头对头比较，结果显示先使用紫杉烷后使用PLD的方案具有显著优势。但不能排除存在偏向一线紫杉烷治疗的选择偏倚，因此需要前瞻性研究验证。
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