Peter Schmid, Javier Cortes, Rebecca Dent, Heather McArthur, Lajos Pusztai, Sherko Kümmel, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Seock-Ah Im, Michael Untch, Peter A Fasching, Marie-Ange Mouret-Reynier, Theodoros Foukakis, Marta Ferreira, Fatima Cardoso, Xuan Zhou, Vassiliki Karantza, Konstantinos Tryfonidis, Gursel Aktan, Joyce O'Shaughnessy
{"title":"Pembrolizumab 治疗早期三阴性乳腺癌的总生存率","authors":"Peter Schmid, Javier Cortes, Rebecca Dent, Heather McArthur, Lajos Pusztai, Sherko Kümmel, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Seock-Ah Im, Michael Untch, Peter A Fasching, Marie-Ange Mouret-Reynier, Theodoros Foukakis, Marta Ferreira, Fatima Cardoso, Xuan Zhou, Vassiliki Karantza, Konstantinos Tryfonidis, Gursel Aktan, Joyce O'Shaughnessy","doi":"10.1056/NEJMoa2409932","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.</p><p><strong>Methods: </strong>We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response and event-free survival. Overall survival was a secondary end point.</p><p><strong>Results: </strong>Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. At the data-cutoff date (March 22, 2024), the median follow-up was 75.1 months (range, 65.9 to 84.0). The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002). Adverse events were consistent with the established safety profiles of pembrolizumab and chemotherapy.</p><p><strong>Conclusions: </strong>Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with neoadjuvant chemotherapy alone, in overall survival among patients with early-stage triple-negative breast cancer. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":" ","pages":"1981-1991"},"PeriodicalIF":96.2000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.\",\"authors\":\"Peter Schmid, Javier Cortes, Rebecca Dent, Heather McArthur, Lajos Pusztai, Sherko Kümmel, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Seock-Ah Im, Michael Untch, Peter A Fasching, Marie-Ange Mouret-Reynier, Theodoros Foukakis, Marta Ferreira, Fatima Cardoso, Xuan Zhou, Vassiliki Karantza, Konstantinos Tryfonidis, Gursel Aktan, Joyce O'Shaughnessy\",\"doi\":\"10.1056/NEJMoa2409932\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.</p><p><strong>Methods: </strong>We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response and event-free survival. Overall survival was a secondary end point.</p><p><strong>Results: </strong>Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. At the data-cutoff date (March 22, 2024), the median follow-up was 75.1 months (range, 65.9 to 84.0). The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002). Adverse events were consistent with the established safety profiles of pembrolizumab and chemotherapy.</p><p><strong>Conclusions: </strong>Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with neoadjuvant chemotherapy alone, in overall survival among patients with early-stage triple-negative breast cancer. 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引用次数: 0
摘要
研究背景在早期三阴性乳腺癌患者中，3期KEYNOTE-522试验显示，在含铂化疗基础上加用pembrolizumab可显著改善病理完全反应和无事件生存期。我们在此报告总生存期的最终结果：我们以2:1的比例随机分配既往未经治疗的II期或III期三阴性乳腺癌患者接受新辅助治疗，即每3周4个周期的pembrolizumab（剂量为200毫克）或安慰剂加紫杉醇和卡铂，然后是4个周期的pembrolizumab或安慰剂加多柔比星-环磷酰胺或表柔比星-环磷酰胺。明确手术后，患者接受每3周一次的pembrolizumab（pembrolizumab-化疗组）或安慰剂（安慰剂-化疗组）辅助治疗，最多9个周期。主要终点是病理完全反应和无事件生存期。总生存期是次要终点：在接受随机分组的1174名患者中，784人被分配到pembrolizumab化疗组，390人被分配到安慰剂化疗组。截至数据截止日（2024年3月22日），中位随访时间为75.1个月（65.9至84.0个月）。pembrolizumab化疗组60个月的估计总生存率为86.6%（95%置信区间[CI]，84.0至88.8），而安慰剂化疗组为81.7%（95%置信区间[CI]，77.5至85.2）（P = 0.002）。不良事件与pembrolizumab和化疗的既定安全性特征一致：结论：与单纯新辅助化疗相比，新辅助pembrolizumab加化疗后再辅助pembrolizumab可显著提高早期三阴性乳腺癌患者的总生存率。(由默克公司的子公司默沙东（Merck Sharp and Dohme）[Rahway, NJ]资助；KEYNOTE-522 ClinicalTrials.gov 编号：NCT03036488）。
Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.
Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.
Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response and event-free survival. Overall survival was a secondary end point.
Results: Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. At the data-cutoff date (March 22, 2024), the median follow-up was 75.1 months (range, 65.9 to 84.0). The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002). Adverse events were consistent with the established safety profiles of pembrolizumab and chemotherapy.
Conclusions: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with neoadjuvant chemotherapy alone, in overall survival among patients with early-stage triple-negative breast cancer. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.).
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