Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia The PEONY Phase 3 Randomized Clinical Trial
Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia The PEONY Phase 3 Randomized Clinical Trial
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帕妥珠单抗、曲妥珠单抗和多西他赛治疗亚洲早期或局部晚期ERBB 2阳性乳腺癌患者的疗效、安全性和耐受性：PEONY III期随机临床试验
DOI：
10.1001/jamaoncol.2019.3692
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发表时间：
2020-03-01
期刊：
影响因子：
28.4
通讯作者：
Eng-Wong, Jennifer
中科院分区：
文献类型：
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作者：
Shao, Zhimin;Pang, Da;Eng-Wong, Jennifer
问：与安慰剂、曲妥珠单抗和多西紫杉醇相比，早期或局部晚期乳腺癌ERBB2阳性的亚洲患者在新辅助治疗环境中加用pertuzumab和曲妥珠单抗和多西紫杉醇是否会受益？在这项对329名早期或局部晚期乳腺癌妇女进行的随机临床试验中，培妥珠单抗的总病理完全缓解率为39.3%，安慰剂为21.8%，两者有显著差异。两组之间的安全数据大体上具有可比性。这意味着在新辅助治疗环境中，与安慰剂、曲妥珠单抗和多西紫杉醇相比，Pertuzumab、曲妥珠单抗和多西紫杉醇显著提高了总的病理完全应答率；这项研究增加了显示pertuzumab方案益处的全部数据。在特定种族群体的全球临床试验中，对已知有益于患者的治疗进行重要的前瞻性评估是至关重要的。目的比较亚洲早期或局部晚期乳腺癌ERBB2阳性患者联合曲妥珠单抗和多西紫杉醇与安慰剂、曲妥珠单抗和多西紫杉醇联合治疗的有效性、安全性和耐受性。设计、设置和参与者这项多中心、双盲、安慰剂对照的3期试验从2016年3月14日至2017年3月13日招募了329名早期ERBB2阳性(T2-3，N0-1，M0)或局部晚期乳腺癌(T2-3，N2或N3，M0；T4，任何N，M0)且原发肿瘤大于2厘米的女性。主要终点的分析是在意向治疗的基础上进行的。干预：术前患者每3周接受4个周期的静脉注射pertuzumab(840 mg负荷量和420 mg维持量)、曲妥珠单抗(8 mg/kg负荷量和6 mg/kg维持量)和多西紫杉醇(75 mg/m(2))或静脉注射安慰剂、曲妥珠单抗和多西紫杉醇。手术后，患者接受3个周期的静脉注射氟尿嘧啶、表阿霉素和环磷酰胺，然后接受13个周期的相同的静脉抗ERBB2治疗(pertuzumab和曲妥珠单抗或安慰剂和曲妥珠单抗)长达1年。主要结果和指标主要终点是独立审查委员会评估的总病理完全应答率。双侧Cochran-Mantel-Haenszel检验按疾病类别和激素受体状态分层，用于比较治疗组之间的发病率。结果总共有329名女性患者被随机分为两组(pertuzumab，219人；安慰剂，110人；平均[SD]年龄，48.8[9.5]岁)。在意向治疗人群中，pertuzumab组的总病理完全应答率为39.3%(86/219)，而安慰剂组为21.8%(24/110)(差异，17.5%[95%CI，6.9%-28.0%]；P=.001)。在最常见的3级或更高级别的不良事件中，pertuzumab组中性粒细胞减少症的发生率较高(218例中83例[38.1%]，110例中36例[32.7%])。在pertuzumab组和安慰剂组分别有10.1%(22/218)和8.2%(9/110)的患者报告了严重不良事件。结论与安慰剂、曲妥珠单抗和多西紫杉醇相比，在亚洲患者中，使用pertuzumab、曲妥珠单抗和多西紫杉醇进行新辅助治疗ERBB2阳性早期或局部晚期乳腺癌的总病理完全应答率在统计学上有显著改善。安全性数据与已知的pertuzumab安全性概况一致，并且在治疗组之间通常具有可比性。牡丹试验增加了显示pertuzumab方案益处的全部数据。这项3期随机临床试验比较了在ERBB2阳性的早期或局部晚期乳腺癌患者中，在曲妥珠单抗和多西紫杉醇的基础上加用pertuzumab与安慰剂、曲妥珠单抗和多西紫杉醇的有效性、安全性和耐受性。
Question Do Asian patients with ERBB2-positive early or locally advanced breast cancer benefit from the addition of pertuzumab to trastuzumab and docetaxel in the neoadjuvant setting, compared with placebo, trastuzumab, and docetaxel? Findings In this randomized clinical trial of 329 women with early or locally advanced breast cancer, total pathologic complete response rates were 39.3% with pertuzumab and 21.8% with placebo, a significant difference. Safety data were generally comparable between groups. Meaning Pertuzumab, trastuzumab, and docetaxel significantly improved total pathologic complete response rate vs placebo, trastuzumab, and docetaxel in the neoadjuvant setting; this study adds to the totality of the data showing the benefit of the pertuzumab regimen.Importance Prospective assessment of treatments known to benefit patients in global clinical trials in specific racial groups is essential. Objective To compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer. Design, Setting, and Participants This multicenter, double-blind, placebo-controlled phase 3 trial enrolled 329 women with ERBB2-positive early (T2-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) and primary tumor larger than 2 cm from March 14, 2016, to March 13, 2017. Analysis of the primary end point was performed on an intention-to-treat basis. Interventions Before surgery, patients received 4 cycles of intravenous pertuzumab (840-mg loading dose and 420-mg maintenance doses), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), and docetaxel (75 mg/m(2)) or intravenous placebo, trastuzumab, and docetaxel every 3 weeks. After surgery, patients received 3 cycles of intravenous fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of the same intravenous anti-ERBB2 therapy (pertuzumab and trastuzumab or placebo and trastuzumab) for up to 1 year. Main Outcomes and Measures The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by disease category and hormone receptor status, was used to compare rates between treatment groups. Results In total, 329 female patients were randomized (pertuzumab, 219; and placebo, 110; mean [SD] age, 48.8 [9.5] years). In the intention-to-treat population, total pathologic complete response rates were 39.3% (86 of 219) in the pertuzumab group and 21.8% (24 of 110) in the placebo group (difference, 17.5% [95% CI, 6.9%-28.0%]; P = .001). Of the most common grade 3 or higher adverse events, there was a higher incidence of neutropenia in the pertuzumab group (83 of 218 [38.1%] vs 36 of 110 [32.7%]). Serious adverse events were reported in 10.1% of patients (22 of 218) in the pertuzumab group and 8.2% of patients (9 of 110) in the placebo group. Conclusions and Relevance Treatment with pertuzumab, trastuzumab, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trastuzumab, and docetaxel for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients. Safety data were in line with the known pertuzumab safety profile and generally comparable between treatment groups. The PEONY trial adds to the totality of data showing the benefit of the pertuzumab regimen.This phase 3 randomized clinical trial compares the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer.