肿瘤

HR-/HER2 早期乳腺癌新辅助降阶梯治疗双靶加减紫杉醇周疗的生物标记物和生存结果报告

作者:会飞的大胖纸 来源:医学论坛网 日期:2021-06-30
导读

         背景: 选择性降阶梯治疗特别是豁免化疗在 HER+ 性早期乳腺癌中生存获益数据有限, ADAPT-HR-/HER2 前期研究结果显示,在 HR-/ HER2+早期乳腺癌中新辅助紫杉醇治疗 12 周加双靶 pCR 率可达 90%,单独使用 PT 治疗具有实质性和临床意义的 pCR 率为 34%。此次第一次报告生存数据。 Background: Optimal use of de-escalate

关键字:  肿瘤 

背景: 选择性降阶梯治疗特别是豁免化疗在 HER+ 性早期乳腺癌中生存获益数据有限, ADAPT-HR-/HER2 前期研究结果显示,在 HR-/ HER2+早期乳腺癌中新辅助紫杉醇治疗 12 周加双靶 pCR 率可达 90%,单独使用 PT 治疗具有实质性和临床意义的 pCR 率为 34%。此次第一次报告生存数据。

 

Background: Optimal use of de-escalated, particularly chemotherapy(CT)-free, neoadjuvant regimens in HER2+ early breast cancer (EBC) is currently unclear as there are limited survival data so far. In ADAPT-HR-/HER2+, we previously showed an excellent pCR rate of 90% after 12-week neoadjuvant paclitaxel (Pac) +pertuzumab (P) +trastuzumab (T) and a substantial and clinically meaningful pCR rate of 34% after P+T alone in HR-/HER2+ EBC. Here, we present first survival data.

 

方法:前瞻性多中心 WSG-ADAPT-HR-/HER2Ⅱ期试验是 ADAP 伞形研究的一部分。共 134 例cT1-cT4c、cN0-3 HR-/HER2 乳腺癌患者随机分配至 4 个周期 pertuzumab+trastuzumabPT 加减紫衫 d1、8、15q3w 两组。所有肿瘤 HR 阴性(ER 和 PR<1%),HER2 阳性(中心实验室,2+ FISH检测阳性,免疫组化 3+)。主要研究终点为 pCR(ypT0/is/ypN0);此研究旨在比较 P+T+pac 组与单纯 P+T 组的 pCR 及早期治疗应答反应(定义为低细胞数和/或 3 周后 Ki67 下降>30%)。由于在 P+T+pac 臂中观察到 pCR 优越性,试验提前停止。次要终点包括安全性、5-年 DFS、OS和转化研究。应用 Cox 回归分析。采用 BC360 量表评估 PAM50 亚型。

 

Methods: The prospective multicenter WSG-ADAPT-HR-/HER2+ phase II-trial is part of the ADAPT-umbrella protocol. Patients with cT1-cT4c, cN0-3 HR-/HER2+ EBC (n = 134) were randomized to 4 cycles of P+T +/- pac d1,8,15 q3w. All tumors were HR-negative (ER and PR < 1%) and HER2-positive (central lab, i.e., 2+ FISH positive or 3+ by immunohistochemistry. Primary endpoint was pCR (ypT0/is/ypN0); omission of further CT was allowed in pts with pCR. Trial objective was to compare pCR in P+T+pac arm vs. early responders in P+T arm (defined as low cellularity and/or Ki67 decrease >30% after 3 weeks). The trial was stopped early due to the observed pCR superiority in the P+T+pac arm. Secondary endpoints included safety, 5-y (distant)-DFS, OS and translational research. Cox-regression analysis was applied. PAM50 subtype was assessed using the BC360 panel.

 

结果:134 例患者随机分 P+T 组(92 例)和 P+T+pac 组(42 例),60%患者 cT2-4, 42%患者淋巴结阳性。中位随访 5 年,研究组之间在 DFS、dDFS 和 OS 方面无显著差异;整个 ITT 人群中仅观察到 13 例 iDFS 事件(7 例 DDF)。12 周治疗后 pCR 组患者及 non-pCR 患者(不考虑 study arm)与 iDFS 改善密切相关(5yDFS 98.5%与 82%,HR=0.14,95%CI0.03-0.64)。在 69 例 pCR患者中,39 例(56.5%)未接受进一步 CT(P+T 组:n=9,29%;P+T+pac 组:n=30,79%),在这些患者中仅观察到 1 例远处复发(1.4%)。在无化疗的的 P+T 组中,HER2 低表达(IHC1/2和 FISH 阳性)和/或 PAM50 基底样亚型患者(n=17,19%)未观察到 pCR。在整体研究人群中,HER2 低表达和/或无早期反应与更差 dDFS(p=0.029)和 iDFS(p=0.068)密切相关。没有观察到新的安全信号。

 

Results: 134 patients were randomized to P+T (n = 92) or P+T+pac (n = 42). 60% of tumors were cT2-4, 42% clinically node-positive. After a median follow-up of 5 years, no significant differences between study arms were observed regarding DFS, dDFS, and OS; only 13 iDFS events (7 dDFS) were observed in the whole ITT population. pCR (vs. non-pCR) after the 12-week study treatment (irrespective of study arm) was strongly associated with improved iDFS (5y DFS 98.5% vs. 82%, HR = 0.14, 95% CI 0.03-0.64). Of the 69 patients with pCR, 39 (56.5%) received no further CT (P+T arm: n = 9, 29% vs. (P+T+pac arm n = 30, 79%); only 1 distant relapse (1.4%) was observed in these patients. In the CT-free P+T arm, no pCR was observed in patients with low HER2 expression (IHC 1+/2+ and FISH positive) and/or basal-like subtype by PAM50 (n = 17, 19%). In the total study population, low HER2 expression and/or no early response was strongly associated with worse dDFS (p =.029) and iDFS (p =.068). No new safety signals were observed.

 

结论:在前瞻性多中心研究中,首次显示无论是否行进一步化疗,新辅助降阶梯治疗 CT+P+T都有良好的 PCR 及生存 。无化疗方案的治疗方案可能需要选取(例如 HER2 高表达/非基底样肿瘤)的患者。ADAPT HR-/HER2+研究中,12 周期 P+T+pac 治疗后 pCR 与预后改善密切相关,因此可以作为进一步(降阶梯)治疗的预测性指标。

 

Conclusions: For the first time, we have shown both excellent pCR and survival in patients treated by de-escalated neoadjuvant CT+P+T irrespective of further CT use in a prospective multicenter study. Investigation of CT-free regimens may need to be focussed on selected patients only (e.g. with high HER2 expression/non-basal-like tumors). In ADAPT HR-/HER2+, early pCR after only 12 weeks of neoadjuvant P+T+pac was strongly associated with improved outcome and may thus serve as a predictive clinical marker for further treatment (de)-escalation.

 

分享:

评论

我要跟帖
发表
回复 小鸭梨
发表

copyright©医学论坛网 版权所有,未经许可不得复制、转载或镜像

京ICP证120392号  京公网安备110105007198  京ICP备10215607号-1  (京)网药械信息备字(2022)第00160号
//站内统计 //百度统计 //谷歌统计 //站长统计
*我要反馈: 姓    名: 邮    箱: