仑伐替尼联合帕博利珠单抗治疗晚期子宫内膜癌。
Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.
机构信息
From the Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York (V.M.); the European Institute of Oncology IRCCS, University of Milan-Bicocca, Milan (N.C.), Istituto Nazionale Tumori IRCCS-Fondazione G. Pascale, Naples (S.P.), and Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Catholic University of the Sacred Heart, Rome (D.L.) - all in Italy; San Carlos University Teaching Hospital (A.C.H.) and Hospital Universitario Ramón y Cajal (E.M.G.) - both in Madrid; Yale University School of Medicine, New Haven, CT (A.D. Santin); Gustave Roussy Cancerology Institute, Groupe d'Investigateurs Nationaux pour l'Étude des Cancers Ovariens (GINECO), Villejuif (E.C.), and Centre Léon-Bérard, University Claude Bernard, GINECO, Lyon (I.R.-C.) - both in France; the University of Texas Southwestern Medical Center, Dallas (D.S.M.); Saitama Medical University International Medical Center, Hidaka (K.F.), Kurume University School of Medicine, Kurume (K.U.), Aichi Cancer Center Hospital, Nagoya (J.S.), and National Cancer Center Hospital-Kokuritsu Gan Kenkyu Center Chuo Byoin, Tokyo (K.Y.) - all in Japan; Royal North Shore Hospital, St. Leonards, NSW, Australia (S.B.-H.); Sheba Medical Center, Ramat Gan, Israel (R.S.-F.); Asan Medical Center, University of Ulsan, Seoul, South Korea (Y.-M.K.); Ege University, Izmir, Turkey (U.A.S.); University College London Hospitals NHS Foundation Trust, London (M.M.M.), and Eisai, Hatfield (A.D. Smith) - both in the United Kingdom; and Merck, Kenilworth (S.K., S.B., R.J.O.), and Eisai, Woodcliff Lake (L.D.) - both in New Jersey.
出版信息
N Engl J Med. 2022 Feb 3;386(5):437-448. doi: 10.1056/NEJMoa2108330. Epub 2022 Jan 19.
BACKGROUND
Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear.
METHODS
In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed.
RESULTS
A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembrolizumab and in 72.7% of those who received chemotherapy.
CONCLUSIONS
Lenvatinib plus pembrolizumab led to significantly longer progression-free survival and overall survival than chemotherapy among patients with advanced endometrial cancer. (Funded by Eisai and Merck Sharp and Dohme [a subsidiary of Merck]; Study 309-KEYNOTE-775 ClinicalTrials.gov number, NCT03517449.).
背景
铂类化疗失败后晚期子宫内膜癌的标准治疗仍不明确。
方法
在这项 3 期临床试验中，我们以 1:1 的比例随机分配先前接受过至少一种铂类化疗方案治疗的晚期子宫内膜癌患者，接受仑伐替尼（20mg，每日口服 1 次）加帕博利珠单抗（200mg，每 3 周静脉输注 1 次）或医生选择的化疗（阿霉素 60mg/m2，每 3 周静脉输注 1 次，或紫杉醇 80mg/m2，每周静脉输注 1 次[3 周为 1 个周期，1 周为休息期]）。主要终点是根据实体瘤反应评估标准 1.1 进行盲法独立中心评估的无进展生存期和总生存期。在错配修复功能完整（pMMR）疾病患者和所有患者中评估了终点。还评估了安全性。
结果
共有 827 名患者（697 名 pMMR 疾病患者和 130 名错配修复缺陷疾病患者）被随机分配接受仑伐替尼加帕博利珠单抗（411 名患者）或化疗（416 名患者）。仑伐替尼加帕博利珠单抗组的无进展生存期长于化疗组（pMMR 人群：6.6 个月 vs. 3.8 个月；进展或死亡风险比，0.60；95%置信区间[CI]，0.50 至 0.72；P<0.001；总体：7.2 个月 vs. 3.8 个月；风险比，0.56；95%CI，0.47 至 0.66；P<0.001）。仑伐替尼加帕博利珠单抗组的总生存期长于化疗组（pMMR 人群：17.4 个月 vs. 12.0 个月；死亡风险比，0.68；95%CI，0.56 至 0.84；P<0.001；总体：18.3 个月 vs. 11.4 个月；风险比，0.62；95%CI，0.51 至 0.75；P<0.001）。仑伐替尼加帕博利珠单抗组 88.9%的患者和化疗组 72.7%的患者发生 3 级或更高级别的不良事件。
结论
在晚期子宫内膜癌患者中，仑伐替尼加帕博利珠单抗治疗组的无进展生存期和总生存期明显长于化疗组。（由卫材和默克密理博[默克的子公司]资助；Study 309-KEYNOTE-775，ClinicalTrials.gov 编号，NCT03517449。）
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