From Dana-Farber Cancer Institute, Boston (T.K.C.); Poznan University of Medical Sciences, Poznan (P.T.), and Wojewódzki Szpital Zespolony im. L. Rydygiera w Toruniu, Torun (P.S.) - both in Poland; Sungkyunkwan University, Samsung Medical Center (S.H.P.), and Asan Medical Center, University of Ulsan College of Medicine (J.L.L.) - both in Seoul, South Korea; Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow (B.V.), Edinburgh Cancer Centre and University of Edinburgh, Edinburgh (S.N.S.), and Imperial College Healthcare NHS Trust (N.S.) and the Royal Free Hospital NHS Trust, University College London (T.P.), London - all in the United Kingdom; Fiona Stanley Hospital, Perth, WA (T.F.), and Macquarie University, Sydney (H.G.) - both in Australia; Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H.C.); Fakultni Nemocnice Ostrava, Ostrava (J.H.), and Palacký University and University Hospital Olomouc, Olomouc (B.M.) - both in the Czech Republic; University Hospital Jean Minjoz, Besançon (A.T.-V.), University Hospital Bordeaux-Hôpital Saint-André, Bordeaux (M.G.-G.), Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse (C.C.), Centre Hospitalier Universitaire de Montpellier, Montpellier (D.T.), and Hôpital Européen Georges Pompidou, University of Paris, Paris (S.O.) - all in France; Fundación Arturo López Pérez, Santiago, Chile (M.M.); Abramson Cancer Center, Philadelphia (N.H.); Omsk Clinical Oncology Dispensary, Omsk, Russia (E.K.); the University of Michigan, Ann Arbor (A.A.); Rocky Mountain Cancer Centers and U.S. Oncology Research, Denver (J.M.B.); Texas Oncology, U.S. Oncology Research, Woodlands (G.D.), and the University of Texas Southwestern, Dallas (H.H.); the University of Toyama, Toyama, Japan (H.K.); Eberhard Karls University Tübingen, Tübingen, Germany (J.B.); Merck, Kenilworth, NJ (R.F.P., P.Z., K.I., J.W.-R.); and USC Norris Comprehensive Cancer Center, Los Angeles (D.I.Q.).
N Engl J Med. 2021 Aug 19;385(8):683-694. doi: 10.1056/NEJMoa2106391.
Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence.
In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point.
A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred.
Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).
接受肾切除术的肾细胞癌患者在降低复发风险方面没有高证据支持的辅助治疗选择。
在一项双盲、3 期临床试验中，我们以 1:1 的比例随机分配接受肾切除术且有复发高风险（伴或不伴转移切除术）的透明细胞肾细胞癌患者，接受静脉注射辅助派姆单抗（剂量为 200mg）或安慰剂，每 3 周一次，最多 17 个周期（约 1 年）。主要终点是根据研究者评估的无病生存期。总生存期是一个关键次要终点。安全性是次要终点。
共有 496 名患者被随机分配接受派姆单抗治疗，498 名患者接受安慰剂治疗。在预设的中期分析中，从随机分组到数据截止日期的中位时间为 24.1 个月。与安慰剂相比，派姆单抗治疗显著延长了无病生存期（24 个月时无病生存率，77.3%比 68.1%；复发或死亡的风险比，0.68；95%置信区间[CI]，0.53 至 0.87；P=0.002[双侧]）。派姆单抗组和安慰剂组 24 个月时的估计生存率分别为 96.6%和 93.5%（死亡风险比，0.54；95%CI，0.30 至 0.96）。接受派姆单抗治疗的患者中任何原因导致的 3 级或更高的不良事件发生率为 32.4%，接受安慰剂治疗的患者为 17.7%。没有与派姆单抗治疗相关的死亡。
与安慰剂相比，在有高复发风险的肾细胞癌患者中，手术后使用派姆单抗治疗可显著改善无病生存期。（由默克公司的子公司默克夏普和多姆资助；KEYNOTE-564 临床试验.gov 编号，NCT03142334）。
