两周来曲唑治疗后 Ki67 缓解的激素受体阳性/人表皮生长因子受体 2 阴性乳腺癌患者的降阶梯治疗：PerELISA 新辅助研究结果。

De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2-week letrozole: results of the PerELISA neoadjuvant study.

机构信息

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova; Medical Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova.

出版信息

Ann Oncol. 2019 Jun 1;30(6):921-926. doi: 10.1093/annonc/mdz055.

DOI:10.1093/annonc/mdz055

PMID:30778520

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6594455/

Abstract

BACKGROUND

In human epidermal growth factor receptor 2 (HER2+) breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive versus negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-week letrozole.

PATIENTS AND METHODS

PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Patients received 2-week letrozole, and then underwent re-biopsy for Ki67 evaluation. Patients classified as molecular responders (Ki67 relative reduction >20% from baseline) continued letrozole and started trastuzumab-pertuzumab for five cycles. Patients classified as molecular non-responders started weekly paclitaxel for 13 weeks combined with trastuzumab-pertuzumab. Primary aim was breast and axillary pCR. According to a two-stage Simon's design, to reject the null hypothesis, at least 8/43 pCR had to be documented.

RESULTS

Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95% confidence interval 11.1% to 34.5%). Among molecular non-responders, 16/17 completed treatment and underwent surgery, with pCR observed in 81.3% of the cases. PAM50 intrinsic subtype was significantly associated with Ki67 response and pCR. Among molecular responders, the pCR rate was significantly higher in HER2-enriched than in other subtypes (45.5% versus 13.8%, P = 0.042).

CONCLUSIONS

The primary end point of the study was met, by reaching the pre-specified pCRs. In patients selected using Ki67 reduction after short-term letrozole exposure, a meaningful pCR rate can be achieved without chemotherapy. PAM50 intrinsic subtyping further refines our ability to identify a subset of patients for whom chemotherapy might be spared.

EUDRACT NUMBER

2013-002662-40.

CLINICALTRIALS.GOV IDENTIFIER: NCT02411344.

摘要

背景

在人表皮生长因子受体 2（HER2+）乳腺癌中，新辅助化疗加抗 HER2 治疗的试验显示，激素受体（HR）阳性肿瘤的病理完全缓解（pCR）率明显低于 HR 阴性肿瘤。PerELISA 研究旨在评估一种降阶梯、无化疗的新辅助方案在基于 2 周来曲唑后 Ki67 抑制选择的 HR+/HER2+乳腺癌患者中的疗效。

患者和方法

PerELISA 是一项针对绝经后 HR+/HER2+可手术乳腺癌患者的 II 期、多中心研究。患者接受 2 周来曲唑治疗，然后进行 Ki67 评估的再活检。将 Ki67 相对基线降低>20%的患者归类为分子应答者，继续接受来曲唑治疗，并开始曲妥珠单抗-帕妥珠单抗治疗 5 个周期。将 Ki67 无应答者归类为开始每周紫杉醇治疗 13 周，同时联合曲妥珠单抗-帕妥珠单抗治疗。主要目的是乳房和腋窝 pCR。根据 Simon 的两阶段设计，为了拒绝零假设，必须至少有 8/43 例 pCR 被记录。

结果

共纳入 64 例患者，44 例被归类为分子应答者。所有这些患者都完成了来曲唑-曲妥珠单抗-帕妥珠单抗的治疗，并接受了手术。44 例患者中有 9 例（20.5%，95%置信区间 11.1%至 34.5%）达到 pCR。在分子无应答者中，17 例中有 16 例完成了治疗并接受了手术，其中 81.3%的患者达到了 pCR。PAM50 内在亚型与 Ki67 反应和 pCR 显著相关。在分子应答者中，HER2 富集亚型的 pCR 率明显高于其他亚型（45.5%比 13.8%，P=0.042）。