曲妥珠单抗-美坦新偶联物和帕妥珠单抗联合用于人表皮生长因子受体 2 阳性乳腺癌：III 期 KRISTINE 研究的 3 年结果。

Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study.

机构信息

University of California, Los Angeles, Los Angeles, CA.

Universidad Complutense, CUBERONC, GEICAM, Madrid, Spain.

出版信息

J Clin Oncol. 2019 Sep 1;37(25):2206-2216. doi: 10.1200/JCO.19.00882. Epub 2019 Jun 3.

DOI:10.1200/JCO.19.00882

PMID:31157583

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6774816/

Abstract

PURPOSE

The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% 55.7%; = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE.

METHODS

Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery).

RESULTS

Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% 9.9%) and AEs leading to treatment discontinuation (18.4% 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment.

CONCLUSION

Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.

摘要

目的

KRISTINE 研究比较了新辅助曲妥珠单抗-美坦新偶联物（T-DM1+P）联合多西他赛、卡铂、曲妥珠单抗联合 P（TCH+P）治疗人表皮生长因子受体 2 阳性 II 至 III 期乳腺癌。T-DM1+P 导致较低的病理完全缓解率（44.4% 比 55.7%；.016），但 3 级或更高级别和严重不良事件（AE）较少。这里，我们报告 KRISTINE 的 3 年结果。

方法

患者每 3 周接受 6 个周期的新辅助 T-DM1+P 或 TCH+P 治疗。接受 T-DM1+P 的患者继续接受辅助 T-DM1+P 治疗，接受 TCH+P 的患者接受辅助曲妥珠单抗联合 pertuzumab 治疗。次要终点包括无事件生存（EFS）、总生存、患者报告结果（从随机分组开始测量）和无侵袭性疾病生存（IDFS；从手术开始测量）。

结果

共有 444 例患者被随机分配（T-DM1+P，n=223；TCH+P，n=221）。中位随访时间为 37 个月。T-DM1+P 组 EFS 事件的风险更高（风险比[HR]，2.61[95%CI，1.36 至 4.98]），手术前局部区域进展事件更多（15[6.7%] 比 0）。手术后 IDFS 事件的风险在两组之间相似（HR，1.11[95%CI，0.52 至 2.40]）。手术后病理完全缓解与 IDFS 事件风险降低相关（HR，0.24[95%CI，0.09 至 0.60]），与治疗臂无关。总体而言，T-DM1+P 组 3 级或更高级别的 AE（31.8% 比 67.7%）较少。在辅助治疗期间，T-DM1+P 组更常见 3 级或更高级别的 AE（24.5% 比 9.9%）和因 AE 而停药（18.4% 比 3.8%）。在新辅助治疗期间，患者报告的结果倾向于 T-DM1+P，在辅助治疗期间与曲妥珠单抗联合 pertuzumab 相似。