Scholarlink

<p>Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER<sup>+</sup>/HER2<sup>−</sup>) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER<sup>+</sup>/HER2<sup>−</sup> grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1–2 or T3–4, cN0–2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W. After surgery (with/without adjuvant radiation therapy), patients received adjuvant pembrolizumab or placebo for nine cycles plus adjuvant endocrine therapy. Dual primary endpoints were pathological complete response and event-free survival in the intention-to-treat population. In total, 635 patients were assigned to the pembrolizumab−chemotherapy arm and 643 to the placebo−chemotherapy arm. At the study’s prespecified first interim analysis, the pathological complete response rate was 24.3% (95% confidence interval (CI), 21.0–27.8%) in the pembrolizumab−chemotherapy arm and 15.6% (95% CI, 12.8–18.6%) in the placebo−chemotherapy arm (estimated treatment difference, 8.5 percentage points; 95% CI, 4.2–12.8; <i>P</i> = 0.00005). Event-free survival was not mature in this analysis. During the neoadjuvant phase, treatment-related adverse events of grade ≥3 were reported in 52.5% and 46.4% of patients in the pembrolizumab−chemotherapy and placebo−chemotherapy arms, respectively. In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients with high-risk, early-stage ER<sup>+</sup>/HER2<sup>−</sup> breast cancer. Safety was consistent with the known profiles of each study treatment. Follow-up continues for event-free survival. ClinicalTrials.gov identifier: <a href="https://clinicaltrials.gov/study/NCT03725059">NCT03725059</a>.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Pembrolizumab and chemotherapy in high-risk, early-stage, ER+/HER2− breast cancer: a randomized phase 3 trial

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月21日

查看全文
  • Fatima Cardoso,
  • Joyce O’Shaughnessy,
  • Zhenzhen Liu,
  • Heather McArthur,
  • Peter Schmid,
  • Javier Cortes,
  • Nadia Harbeck,
  • Melinda L. Telli,
  • David W. Cescon,
  • Peter A. Fasching,
  • Zhimin Shao,
  • Delphine Loirat,
  • Yeon Hee Park,
  • Manuel Gonzalez Fernandez,
  • Gábor Rubovszky,
  • Laura Spring,
  • Seock-Ah Im,
  • Rina Hui,
  • Toshimi Takano,
  • Fabrice André,
  • Hiroyuki Yasojima,
  • Yu Ding,
  • Liyi Jia,
  • Vassiliki Karantza,
  • Konstantinos Tryfonidis,
  • Aditya Bardia

摘要

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2−) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER+/HER2− grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1–2 or T3–4, cN0–2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W. After surgery (with/without adjuvant radiation therapy), patients received adjuvant pembrolizumab or placebo for nine cycles plus adjuvant endocrine therapy. Dual primary endpoints were pathological complete response and event-free survival in the intention-to-treat population. In total, 635 patients were assigned to the pembrolizumab−chemotherapy arm and 643 to the placebo−chemotherapy arm. At the study’s prespecified first interim analysis, the pathological complete response rate was 24.3% (95% confidence interval (CI), 21.0–27.8%) in the pembrolizumab−chemotherapy arm and 15.6% (95% CI, 12.8–18.6%) in the placebo−chemotherapy arm (estimated treatment difference, 8.5 percentage points; 95% CI, 4.2–12.8; P = 0.00005). Event-free survival was not mature in this analysis. During the neoadjuvant phase, treatment-related adverse events of grade ≥3 were reported in 52.5% and 46.4% of patients in the pembrolizumab−chemotherapy and placebo−chemotherapy arms, respectively. In summary, the addition of pembrolizumab to neoadjuvant chemotherapy significantly improved the pathological complete response rate in patients with high-risk, early-stage ER+/HER2− breast cancer. Safety was consistent with the known profiles of each study treatment. Follow-up continues for event-free survival. ClinicalTrials.gov identifier: NCT03725059.