Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.
Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.
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DOI：
10.1056/nejmoa1703643
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发表时间：
2017-07-13
期刊：
影响因子：
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通讯作者：
APHINITY Steering Committee and Investigators
中科院分区：
文献类型：
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作者：
von Minckwitz G;Procter M;de Azambuja E;Zardavas D;Benyunes M;Viale G;Suter T;Arahmani A;Rouchet N;Clark E;Knott A;Lang I;Levy C;Yardley DA;Bines J;Gelber RD;Piccart M;Baselga J;APHINITY Steering Committee and Investigators
帕妥珠单抗增加了术前背景下的病理学完全缓解率，并在与曲妥珠单抗和化疗联合治疗人表皮生长因子受体2（HER 2）阳性乳腺癌时增加了转移性疾病患者的总生存期。在这项试验中，我们研究了帕妥珠单抗，当添加到辅助曲妥珠单抗和化疗，改善与HER 2阳性早期乳腺癌患者的结果。我们将淋巴结阳性或高危淋巴结阴性HER 2阳性、可手术乳腺癌患者随机分配接受帕妥珠单抗或安慰剂加标准辅助化疗加1年曲妥珠单抗治疗。我们假设帕妥珠单抗组3年无侵袭性疾病生存率为91.8%，安慰剂组为89.2%。在试验人群中，随机分配接受帕妥珠单抗（2400例患者）或安慰剂（2405例患者）的患者中有63%患有淋巴结阳性疾病，36%患有受体阴性疾病。帕妥珠单抗组171例患者（7.1%）和安慰剂组210例患者（8.7%）发生疾病复发（风险比，0.81; 95%置信区间[CI]，0.66 - 1.00; P= 0.045）。帕妥珠单抗组3年无侵袭性疾病生存率估计值为94.1%，安慰剂组为93.2%。在淋巴结阳性患者队列中，帕妥珠单抗组的3年无侵袭性疾病生存率为92.0%，而安慰剂组为90.2%（侵袭性疾病事件的风险比为0.77; 95%CI为0.62 - 0.96; P= 0.02）。在淋巴结阴性患者队列中，帕妥珠单抗组3年无侵袭性疾病生存率为97.5%，安慰剂组为98.4%（侵袭性疾病事件的风险比为1.13; 95%CI为0.68 - 1.86; P = 0.64）。心力衰竭、心源性死亡和心功能不全在两个治疗组中均不常见。3级或以上腹泻几乎仅发生在化疗期间，帕妥珠单抗组的发生率高于安慰剂组（9.8% vs. 3.7%）。当帕妥珠单抗与曲妥珠单抗联合化疗时，帕妥珠单抗显著提高了HER 2阳性、可手术乳腺癌患者的无侵袭性疾病生存率。帕妥珠单抗组腹泻比安慰剂组更常见。
Pertuzumab increases the rate of pathological complete response in the preoperative context and increases overall survival among patients with metastatic disease when it is added to trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2 (HER2)–positive breast cancer. In this trial, we investigated whether pertuzumab, when added to adjuvant trastuzumab and chemotherapy, improves outcomes among patients with HER2-positive early breast cancer. We randomly assigned patients with node-positive or high-risk node-negative HER2-positive, operable breast cancer to receive either pertuzumab or placebo added to standard adjuvant chemotherapy plus 1 year of treatment with trastuzumab. We assumed a 3-year invasive-disease–free survival rate of 91.8% with pertuzumab and 89.2% with placebo. In the trial population, 63% of the patients who were randomly assigned to receive pertuzumab (2400 patients) or placebo (2405 patients) had node-positive disease and 36% had hormone-receptor–negative disease. Disease recurrence occurred in 171 patients (7.1%) in the pertuzumab group and 210 patients (8.7%) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.66 to 1.00; P= 0.045). The estimates of the 3-year rates of invasive-disease–free survival were 94.1% in the pertuzumab group and 93.2% in the placebo group. In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease–free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P= 0.02). In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease–free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P = 0.64). Heart failure, cardiac death, and cardiac dysfunction were infrequent in both treatment groups. Diarrhea of grade 3 or higher occurred almost exclusively during chemotherapy and was more frequent with pertuzumab than with placebo (9.8% vs. 3.7%). Pertuzumab significantly improved the rates of invasive-disease–free survival among patients with HER2-positive, operable breast cancer when it was added to trastuzumab and chemotherapy. Diarrhea was more common with pertuzumab than with placebo.