曲妥珠单抗和帕妥珠单抗联合每周紫杉醇新辅助双阻断 12 周治疗 HER2 阳性早期乳腺癌（EBC）的降阶梯策略：WSG-ADAPT HER2+/HR- Ⅱ期试验的最终分析：疗效、安全性和预测标志物。
De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel.
机构信息
West German Study Group GmbH, Moenchengladabach; Evangelical Hospital Johanniter Bethesda, Breast Center Niederrhein, Moenchengladbach.
West German Study Group GmbH, Moenchengladabach; Evangelical Hospital Johanniter Bethesda, Breast Center Niederrhein, Moenchengladbach; University of Cologne, Cologne.
出版信息
Ann Oncol. 2017 Nov 1;28(11):2768-2772. doi: 10.1093/annonc/mdx494.
BACKGROUND
Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy.
PATIENTS AND METHODS
Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T + P ± weekly paclitaxel (pac) at 80 mg/m2. Early response was defined as proliferation decrease ≥30% of Ki-67 (versus baseline) or low cellularity (<500 invasive tumor cells) in the 3-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T + P arm versus all chemotherapy-treated patients.
RESULTS
From February 2014 to December 2015, 160 patients were screened, 92 were randomized to T + P and 42 to T + P+pac. Baseline characteristics were well balanced (median age 54 versus 51.5 years, cT2 51.1 versus 52.4%, cN0 54.3 versus 61.9%); 91.3% of patients completed T + P per protocol and 92.9% T + P+pac. The pCR rate in the T + P+pac arm was 90.5%, compared with 36.3% in the T + P arm as a whole. In the T + P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared with 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92). No new safety signals were observed in the study population.
CONCLUSION
Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared with dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.
背景
曲妥珠单抗（T）联合新辅助化疗治疗人表皮生长因子受体 2（HER2）过表达的早期乳腺癌（EBC）的缓解率得到了提高，加入帕妥珠单抗（P）后进一步提高。前瞻性、Ⅱ期、新辅助 WSG-ADAPT HER2+/HR- 试验评估了仅接受双阻断治疗的患者，如果早期出现强烈应答，是否可能达到与接受双阻断联合化疗的患者相当的病理完全缓解（pCR）。
方法
HER2+/HR-EBC（M0）的女性患者按 5:2 比例随机分配至接受 12 周 T+P±每周 80mg/m2紫杉醇（pac）治疗。早期应答定义为 3 周时活检的 Ki-67 增殖减少≥30%（与基线相比）或细胞密度降低（<500 个浸润性肿瘤细胞）。该试验旨在测试 T+P 组中早期应答患者的 pCR 非劣效性，与所有接受化疗治疗的患者相比。
结果
从 2014 年 2 月至 2015 年 12 月，共筛选了 160 例患者，92 例随机分配至 T+P 组，42 例随机分配至 T+P+pac 组。基线特征均衡（中位年龄 54 岁比 51.5 岁，cT2 51.1%比 52.4%，cN0 54.3%比 61.9%）；91.3%的患者按方案完成 T+P 治疗，92.9%的患者完成 T+P+pac 治疗。T+P+pac 组的 pCR 率为 90.5%，而 T+P 组总体为 36.3%。在 T+P 组中，24/92 例患者被归类为无应答者，其 pCR 率仅为 8.3%，而应答者（38/92）和早期应答未分类者（30/92）的 pCR 率分别为 44.7%和 42.9%。研究人群中未观察到新的安全性信号。
结论
在 12 周新辅助治疗环境中，与单独使用双 HER2 阻断相比，紫杉烷单药联合双 HER2 阻断可显著提高 HER2+/HR-EBC 的 pCR 率，即使在双阻断的早期应答者中也是如此。双阻断治疗的早期无应答强烈预示着无法达到 pCR。
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