De-escalated therapy for HR+/HER2+breast cancer patients with Ki67 response after 2-week letrozole: results of the PerELISA neoadjuvant study
De-escalated therapy for HR+/HER2+breast cancer patients with Ki67 response after 2-week letrozole: results of the PerELISA neoadjuvant study
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DOI：
10.1093/annonc/mdz055
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发表时间：
2019-06-01
影响因子：
50.5
通讯作者：
Conte, P. F.
中科院分区：
文献类型：
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作者：
Guarneri, V;Dieci, M., V;Conte, P. F.
背景 在人表皮生长因子受体 2 (HER2+) 乳腺癌中，化疗加抗 HER2 治疗的新辅助试验一致显示，与阴性肿瘤相比，激素受体 (HR) 阳性肿瘤的病理完全缓解 (pCR) 率较低。 PerELISA 研究旨在评估降级、免化疗新辅助治疗方案对基于来曲唑两周后 Ki67 抑制而选择的 HR+/HER2+ 乳腺癌患者的疗效。 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。患者接受为期 2 周的来曲唑治疗，然后再次进行活检以进行 Ki67 评估。被分类为分子应答者（Ki67 相对基线降低>20%）的患者继续使用来曲唑并开始曲妥珠单抗-帕妥珠单抗五个周期。被归类为分子无反应者的患者开始每周接受紫杉醇联合曲妥珠单抗-帕妥珠单抗治疗，持续 13 周。主要目标是乳房和腋窝 pCR。根据两阶段西蒙的设计，要拒绝零假设，必须记录至少 8/43 pCR。 结果 纳入了 64 名患者，其中 44 名被归类为分子应答者。所有这些患者均完成了来曲唑-曲妥珠单抗-帕妥珠单抗的指定治疗并接受了手术。 9/44 例观察到 pCR（20.5%，95% 置信区间 11.1% 至 34.5%）。在分子无反应者中，16/17 完成治疗并接受手术，其中 81.3% 的病例观察到 pCR。 PAM50 内在亚型与 Ki67 反应和 pCR 显着相关。在分子应答者中，HER2 富集的 pCR 率显着高于其他亚型（45.5% 比 13.8%，P=0.042）。结论 通过达到预先指定的 pCR，达到了研究的主要终点。在短期来曲唑暴露后选择使用 Ki67 降低的患者中，无需化疗即可实现有意义的 pCR 率。 PAM50 内在亚型进一步完善了我们识别可能免于化疗的患者子集的能力。EUDRACT 编号 2013-002662-40ClinicalTrials.gov 标识符 NCT02411344
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 13weeks 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 2013-002662-40ClinicalTrials.gov Identifier NCT02411344