From the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London (P.S.); International Breast Cancer Center, Pangaea Oncology, Quirónsalud Group, and Medical Scientia Innovation Research, Barcelona, and IOB Madrid, Institute of Oncology, Hospital Beata María Ana, and the Faculty of Biomedical and Health Sciences, Department of Medicine, Universidad Europea de Madrid, Madrid - all in Spain (J.C.); National Cancer Center Singapore, Duke-National University of Singapore Medical School, Singapore (R.D.); University of Texas Southwestern Medical Center (H.M.) and Baylor University Medical Center, Texas Oncology, Sarah Cannon Research Institute (J.O.) - both in Dallas; Yale School of Medicine, Yale Cancer Center, New Haven, CT (L.P.); the Breast Unit, Department of Gynecology with Breast Center, Kliniken Essen-Mitte, Essen (S.K.), Charité-Universitätsmedizin Berlin (S.K.) and the Breast Cancer Center, Helios Klinikum Berlin-Buch (M.U.), Berlin, the Institute of Pathology, Philipps University of Marburg and University Hospital Marburg, Marburg (C.D.), the Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Munich, LMU University Hospital, Munich (N.H.), and University Hospital Erlangen, Comprehensive Cancer Center Erlangen-European Metropolitan Region of Nuremberg, Erlangen (P.A.F.) - all in Germany; Samsung Medical Center, Sungkyunkwan University School of Medicine (Y.H.P.), and Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University (S.-A.I.) - both in Seoul, South Korea; Westmead Breast Cancer Institute, Westmead Hospital and the University of Sydney, Sydney (R.H.); the Center of Cancer Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong (R.H.); Hokkaido University Hospital, Sapporo, Japan (M.T.); Centre Jean-Perrin, Clermont-Ferrand, France (M.-A.M.-R.); the Department of Oncology-Pathology, Karolinska Institutet, and Breast Center, Theme Cancer, Karolinska University Hospital, Stockholm (T.F.); Instituto Português de Oncologia do Porto Francisco Gentil, Porto (M.F.), and the Breast Unit, Champalimaud Clinical Center-Champalimaud Foundation, Lisbon (F.C.) - both in Portugal; and the Department of Oncology, Merck, Rahway, NJ (X.Z., V.K., K.T., G.A.).
N Engl J Med. 2024 Nov 28;391(21):1981-1991. doi: 10.1056/NEJMoa2409932. Epub 2024 Sep 15.
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.
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.
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.
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.).
在早期三阴性乳腺癌患者中，III 期 KEYNOTE-522 试验表明，与含铂化疗相比，帕博利珠单抗联合化疗可显著提高病理完全缓解率和无事件生存期。在此，我们报告总生存期的最终结果。
我们以 2:1 的比例随机分配未经治疗的 II 期或 III 期三阴性乳腺癌患者接受新辅助治疗，接受 4 个周期的帕博利珠单抗（剂量为 200mg）或安慰剂，每 3 周一次，联合紫杉醇和卡铂，随后是 4 个周期的帕博利珠单抗或安慰剂联合多柔比星-环磷酰胺或表柔比星-环磷酰胺。在确定性手术后，患者接受辅助帕博利珠单抗（帕博利珠单抗-化疗组）或安慰剂（化疗-安慰剂组），每 3 周一次，最多 9 个周期。主要终点是病理完全缓解和无事件生存期。总生存期是次要终点。
在 1174 名接受随机分组的患者中，784 名患者被分配至帕博利珠单抗-化疗组，390 名患者被分配至化疗-安慰剂组。在数据截止日期（2024 年 3 月 22 日），中位随访时间为 75.1 个月（范围为 65.9 至 84.0）。帕博利珠单抗-化疗组 60 个月的总生存率估计为 86.6%（95%置信区间[CI]，84.0 至 88.8），而化疗-安慰剂组为 81.7%（95% CI，77.5 至 85.2）（P=0.002）。不良事件与帕博利珠单抗和化疗的既定安全性特征一致。
与单纯新辅助化疗相比，新辅助帕博利珠单抗联合化疗加辅助帕博利珠单抗可显著改善早期三阴性乳腺癌患者的总生存期。（由默克公司的子公司默克夏普和多姆公司[新泽西州拉威]资助；KEYNOTE-522 ClinicalTrials.gov 编号，NCT03036488）。
