TRYPHAENA 心脏安全性随机、二期疗效分析：评估曲妥珠单抗和帕妥珠单抗联合标准新辅助含蒽环类和不含蒽环类化疗方案治疗 HER2 阳性早期乳腺癌患者的疗效。
Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer.
机构信息
National Center for Tumor Diseases, University Hospital, Heidelberg, Germany.
British Columbia Cancer Agency - Vancouver Centre, University of British Columbia, Vancouver, Canada.
出版信息
Eur J Cancer. 2018 Jan;89:27-35. doi: 10.1016/j.ejca.2017.10.021. Epub 2017 Dec 8.
BACKGROUND
We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy.
METHODS
Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m 5-fluorouracil/100 mg/m epirubicin/600 mg/m cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m, escalated to 100 mg/m if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989.
RESULTS
Three-year Kaplan-Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79-95), 88% (80-96) and 90% (82-97) in groups A-C, respectively. Progression-free survival (PFS) rates were 89% (81-96), 89% (81-96) and 87% (80-95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11-0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A-C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%.
CONCLUSIONS
Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.
背景
我们报告了曲妥珠单抗联合帕妥珠单抗联合含蒽环类或蒽环类药物化疗新辅助治疗 HER2 阳性早期乳腺癌患者的长期疗效和心脏安全性结果。
方法
对随机分为 A 组（第 1-6 周期：曲妥珠单抗[8mg/kg 负荷剂量和 6mg/kg 维持剂量]联合帕妥珠单抗[840mg 负荷剂量和 420mg 维持剂量]，加 5-氟尿嘧啶、表柔比星和环磷酰胺[FEC] [第 1-3 周期；500mg/m 5-氟尿嘧啶/100mg/m 表柔比星/600mg/m 环磷酰胺]，然后多西他赛[第 4-6 周期；75mg/m，如耐受良好则增加至 100mg/m]）、B 组（第 1-3 周期：FEC，第 4-6 周期：前文所述的曲妥珠单抗联合帕妥珠单抗联合多西他赛）或 C 组（第 1-6 周期：曲妥珠单抗联合帕妥珠单抗联合多西他赛[75mg/m，不增加剂量]，加卡铂[AUC 6]）的患者进行描述性疗效分析，这些患者在最后一名患者随机分组后 5 年进行评估。本研究在 ClinicalTrials.gov 注册，编号为 NCT00976989。
结果
A-C 组患者 3 年无病生存（DFS）的 Kaplan-Meier 生存估计值分别为 87%（95%置信区间：79-95）、88%（80-96）和 90%（82-97）。无进展生存（PFS）率分别为 89%（81-96）、89%（81-96）和 87%（80-95）。总病理完全缓解（tpCR）与无 tpCR 相比，DFS 的无风险比为 0.27（0.11-0.64）。在治疗后随访期间，A-C 组各有 2/72（2.8%）、3/75（4.0%）和 4/76（5.4%）患者出现任何级别的左心室收缩功能障碍；A-C 组各有 8/72（11.1%）、12/75（16.0%）和 9/76（11.8%）患者的左心室射血分数从基线下降≥10%至<50%。
结论
各组间 DFS 和 PFS 相似。达到 tpCR 的患者 DFS 改善。未发现新的安全性信号。
Zotero 插件