DataSheet_2_Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study.docx

BackgroundThe CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS).
MethodsIn this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed.
ResultsBetween Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%).
ConclusionAt 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity.
Trial Registration NumberClinicalTrials.gov reference NCT00563953.

背景：CAPRICE试验旨在专门评估老年患者或存在其他心血管危险因素、无法耐受常规多柔比星治疗者，使用新辅助聚乙二醇化脂质体多柔比星（pegylated liposomal doxorubicin，PLD）的疗效。该研究的初步分析显示，病理完全缓解（pathological complete response，pCR）率为32%，且化疗期间左心室射血分数（left ventricular ejection fraction，LVEF）无显著下降。本文报告该研究的重要次要终点：5年心脏安全性、无病生存期（disease-free survival，DFS）、总生存期（overall survival，OS）及乳腺癌特异性生存期（breast cancer specific survival，BCSS）。

方法：本项多中心单臂Ⅱ期临床试验中，老年患者、易发生心脏毒性者及高危Ⅱ~ⅢB期乳腺癌患者接受新辅助化疗（neoadjuvant chemotherapy，NAC）：每4周给予PLD（35 mg/m²）联合环磷酰胺（600 mg/m²），共4个周期，随后给予12周紫杉醇治疗。分别在基线、治疗期间及治疗后9、16、28、40周检测LVEF、心电图并填写心脏相关问卷。研究的主要终点为pCR，同时分析5年心脏安全性、DFS、BCSS及OS。

结果：2007年10月至2010年6月期间，共纳入50例符合入组标准的患者。患者中位年龄为73岁（范围35~84岁），其中84%的患者年龄超过65岁；64%的患者合并高血压，10%存在既往心脏疾病。大部分肿瘤（88%）为三阴性乳腺癌。未观察到LVEF出现显著下降：基线平均LVEF为66.6%（范围52~86），经中位5年随访后，平均LVEF为66%（范围54.5~73）。在意向治疗人群中，5年DFS率为50%（95%CI 40.2~68.1），5年OS率为56%（95%CI 41.2~68.4）。共发生8例非肿瘤相关死亡，5年BCSS率为67.74%（95%CI：54.31%~81.18%）。

结论：经5年随访，基于PLD的新辅助化疗方案在极高危乳腺癌患者人群中仍保持心脏安全性与有效性，该方案可作为老年患者或存在心脏毒性发病风险者的治疗选择之一。

试验注册号：ClinicalTrials.gov 编号NCT00563953。