BACKGROUND Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear. METHODS In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event-free survival in the intention-to-treat population. RESULTS At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow-up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab-chemotherapy group and 46 of 390 patients (11.8%) in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively. CONCLUSIONS Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy. (Funded by Merck Sharp & Dohme [a subsidiary of Merck]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).

中文翻译：

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Pembrolizumab 用于早期三阴性乳腺癌。

背景 先前的试验表明，在早期三阴性乳腺癌患者中，派姆单抗具有良好的抗肿瘤活性和可接受的安全性。目前尚不清楚在新辅助化疗中添加派姆单抗是否会显着增加早期三阴性乳腺癌患者在最终手术中获得病理完全缓解（定义为乳腺无浸润性癌和淋巴结阴性）的百分比。方法 在这项 3 期试验中，我们随机分配（以 2:1 的比例）既往未经治疗的 II 期或 III 期三阴性乳腺癌患者接受 4 个周期的派姆单抗（剂量为 200 mg）的新辅助治疗。 3 周加紫杉醇和卡铂（784 名患者；pembrolizumab-化疗组）或安慰剂每 3 周加紫杉醇和卡铂（390 名患者；安慰剂-化疗组）；然后两组再接受四个周期的派姆单抗或安慰剂，两组均接受多柔比星-环磷酰胺或表柔比星-环磷酰胺。最终手术后，患者每 3 周接受一次派姆单抗或安慰剂辅助治疗，最多 9 个周期。主要终点是在意向治疗人群中确定手术时的病理完全缓解和无事件生存期。结果 在第一次中期分析中，在接受随机分组的前 602 名患者中，帕博利珠单抗联合化疗组和 51 名病理完全缓解的患者百分比分别为 64.8%（95% 置信区间 [CI]，59.9 至 69.5）。安慰剂化疗组为 2%（95% CI，44.1 至 58.3）（估计治疗差异，13.6 个百分点；95% CI，5.4 至 21.8；P<0.001）。在中位随访 15.5 个月（范围，2.7 至 25.0）后，派姆单抗化疗组 784 名患者中有 58 名（7.4%）和安慰剂化疗组 390 名患者中有 46 名（11.8%）出现疾病进展排除根治性手术，局部或远处复发或第二原发肿瘤，或死于任何原因（风险比，0.63；95% CI，0.43 至 0.93）。在所有治疗阶段，3 级或更高级别的治疗相关不良事件的发生率在派姆单抗化疗组和安慰剂化疗组分别为 78.0% 和 73.0%，包括 0.4%（3 名患者）和 0.3% 的死亡。 1 名患者），分别。结论 在早期三阴性乳腺癌患者中，接受派姆单抗加新辅助化疗的患者病理完全缓解的百分比显着高于接受安慰剂加新辅助化疗的患者。（由 Merck Sharp & Dohme [默克的子公司] 资助；KEYNOTE-522 ClinicalTrials.gov 编号为 NCT03036488。）。