Institut Jules Bordet and L'Université Libre de Bruxelles (ULB), Brussels, Belgium.
Frontier Science Scotland Ltd, Kincraig, Kingussie, United Kingdom.
J Clin Oncol. 2021 May 1;39(13):1448-1457. doi: 10.1200/JCO.20.01204. Epub 2021 Feb 4.
APHINITY, at 45 months median follow-up, showed that pertuzumab added to adjuvant trastuzumab and chemotherapy significantly improved invasive disease-free survival (IDFS) (hazard ratio 0.81 [95% CI, 0.66 to 1.00], = .045) for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), specifically those with node-positive or hormone receptor (HR)-negative disease. We now report the preplanned second interim overall survival (OS) and descriptive updated IDFS analysis with 74 months median follow-up.
After surgery and central HER2-positive confirmation, 4,805 patients with node-positive or high-risk node-negative BC were randomly assigned (1:1) to either 1-year pertuzumab or placebo added to standard adjuvant chemotherapy and 1-year trastuzumab.
This interim OS analysis comparing pertuzumab versus placebo did not reach the = .0012 level required for statistical significance ( = .17, hazard ratio 0.85). Six-year OS were 95% versus 94% with 125 deaths (5.2%) versus 147 (6.1%), respectively. IDFS analysis based on 508 events (intent-to-treat population) showed a hazard ratio of 0.76 (95% CI, 0.64 to 0.91) and 6-year IDFS of 91% and 88% for pertuzumab and placebo groups, respectively. The node-positive cohort continues to derive clear IDFS benefit from pertuzumab (hazard ratio 0.72 [95% CI, 0.59 to 0.87]), 6-year IDFS being 88% and 83%, respectively. Benefit was not seen in the node-negative cohort. In a subset analysis, IDFS benefit from pertuzumab showed a hazard ratio of 0.73 (95% CI, 0.59 to 0.92) for HR-positive disease and a hazard ratio of 0.83 (95% CI, 0.63 to 1.10) for HR-negative disease. Primary cardiac events remain < 1% in both the treatment groups. No new safety signals were seen.
This analysis confirms the IDFS benefit from adding pertuzumab to standard adjuvant therapy for patients with node-positive HER2-positive early BC. Longer follow-up is needed to fully assess OS benefit.
APHINITY 研究中位随访时间为 45 个月，结果显示，与安慰剂加辅助曲妥珠单抗和化疗相比，帕妥珠单抗可显著改善早期人表皮生长因子受体 2（HER2）阳性乳腺癌（BC）患者的浸润性无病生存期（IDFS）（风险比 0.81 [95%CI，0.66 至 1.00]，P =.045），特别是那些淋巴结阳性或激素受体（HR）阴性疾病患者。我们现在报告了预先计划的第二次中期总生存期（OS）和描述性更新的 IDFS 分析，中位随访时间为 74 个月。
在手术后和中心 HER2 阳性确认后，4805 例淋巴结阳性或高危淋巴结阴性 BC 患者被随机（1:1）分配至接受 1 年帕妥珠单抗或安慰剂加标准辅助化疗和 1 年曲妥珠单抗治疗。
与安慰剂相比，该中期 OS 分析未达到统计学意义所需的 =.0012 水平（P =.17，风险比 0.85）。6 年 OS 分别为 95%和 94%，死亡分别为 125 例（5.2%）和 147 例（6.1%）。基于 508 例事件（意向治疗人群）的 IDFS 分析显示，风险比为 0.76（95%CI，0.64 至 0.91），帕妥珠单抗组和安慰剂组的 6 年 IDFS 分别为 91%和 88%。淋巴结阳性队列继续从帕妥珠单抗中获得明确的 IDFS 获益（风险比 0.72 [95%CI，0.59 至 0.87]），6 年 IDFS 分别为 88%和 83%。淋巴结阴性队列未见获益。在亚组分析中，帕妥珠单抗对 HR 阳性疾病的 IDFS 获益的风险比为 0.73（95%CI，0.59 至 0.92），对 HR 阴性疾病的风险比为 0.83（95%CI，0.63 至 1.10）。两组的主要心脏事件均<1%。未发现新的安全信号。
本分析证实，与标准辅助治疗相比，帕妥珠单抗可显著改善淋巴结阳性早期 HER2 阳性 BC 患者的 IDFS。需要更长时间的随访才能充分评估 OS 获益。
