帕博利珠单抗联合化疗治疗晚期子宫内膜癌。
Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.
机构信息
From the Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, Rebecca and John Moores Cancer Center, La Jolla (R.N.E.), and the Kaiser Permanente National Cancer Institute Community Oncology Research Program (NCORP), Antioch Medical Center, Antioch (J.K.) - both in California; the Clinical Trial Development Division, Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo (M.W.S., S.B.L.), the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester (R.G.M.), the Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College, New York (R.E.O., C.A.), and the Northwell Health Cancer Institute, New Hyde Park (V.S.J.) - all in New York; the Case Comprehensive Cancer Center, Cleveland Clinic Foundation, Cleveland (L.B.), and Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus (F.B.); the Pacific Cancer Research Consortium, NCORP, Alaska Women's Cancer Care, and Providence Alaska Cancer Center, Anchorage (J.M.H.); the Pacific Cancer Research Consortium, NCORP, Swedish Medical Center-First Hill, Seattle (F.B.M.); the University of Oklahoma Health Sciences Center, Oklahoma City (R.M.); Jefferson Abington Hospital, Asplundh Cancer Pavilion of Sidney Kimmel Cancer Center, Jefferson Health, Willow Grove, PA (M.S.S.); Georgia NCORP, Atlanta (G.H.C.); Rutgers Cancer Institute of New Jersey, New Brunswick (E.G.); Women and Infants Hospital, Legoretta Cancer Center, Alpert Medical School, Brown University, Providence, RI (C.M.); the University of Alabama at Birmingham-Deep South Research Consortium, O'Neal Comprehensive Cancer Center, University of Alabama Hospital, Birmingham (C.A.L.); Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto (L.T.G.), and the London Regional Cancer Program, London, ON (S.W.) - both in Canada; Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago (E.M.H.); the Indiana University Health Simon Cancer Center, Indianapolis (L.M.L.); the Michigan Cancer Research Consortium, NCORP, Trinity Health IHA Medical Group, Ypsilanti (T.A.B.); the University of Iowa Hospitals and Clinics, Iowa City (E.K.H.); the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis (P.H.T., M.A.P.); and the Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore (A.N.F.).
出版信息
N Engl J Med. 2023 Jun 8;388(23):2159-2170. doi: 10.1056/NEJMoa2302312. Epub 2023 Mar 27.
BACKGROUND
Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear.
METHODS
In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort.
RESULTS
In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy.
CONCLUSIONS
In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).
背景
子宫内膜癌的标准一线化疗是紫杉醇加卡铂。将 pembrolizumab 加入化疗的益处尚不清楚。
方法
在这项双盲、安慰剂对照、随机、3 期临床试验中，我们将 816 名患有可测量疾病（III 期或 IVA 期）或 IVB 期或复发性子宫内膜癌的患者按 1:1 的比例随机分配，接受 pembrolizumab 或安慰剂联合紫杉醇加卡铂联合治疗。pembrolizumab 或安慰剂的给药计划为每 3 周 6 个周期，随后每 6 周最多进行 14 个维持周期。根据患者是否存在错配修复缺陷（dMMR）或错配修复功能正常（pMMR）疾病，将患者分为两个队列。如果无治疗间隔至少为 12 个月，则允许使用辅助化疗。主要终点是两个队列的无进展生存期。在 dMMR 队列中至少发生 84 例死亡或进展事件，在 pMMR 队列中至少发生 196 例事件后，计划进行中期分析。
结果
在 12 个月的分析中，pembrolizumab 组 dMMR 队列的无进展生存估计值为 74%，安慰剂组为 38%（进展或死亡的风险比，0.30；95%置信区间[CI]，0.19 至 0.48；P<0.001），相对风险差异为 70%。在 pMMR 队列中，pembrolizumab 组中位无进展生存期为 13.1 个月，安慰剂组为 8.7 个月（风险比，0.54；95%CI，0.41 至 0.71；P<0.001）。pembrolizumab 和联合化疗的不良反应与预期相符。
结论
在晚期或复发性子宫内膜癌患者中，与单独化疗相比，pembrolizumab 联合标准化疗可显著延长无进展生存期。（由美国国立癌症研究所等资助；NRG-GY018 ClinicalTrials.gov 编号，NCT03914612。）
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