派姆单抗联合阿昔替尼对比舒尼替尼用于晚期肾细胞癌。
Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.
机构信息
From the Cleveland Clinic Taussig Cancer Institute, Cleveland (B.I.R.); Fox Chase Cancer Center, Philadelphia (E.R.P.); Dnipropetrovsk Medical Academy of Ministry of Health of Ukraine (V.S.) and Dnipropetrovsk Medical Academy (I.B.), Dnipro, Sumy State University, Sumy Regional Oncology Center, Sumy (I.V.), and Ivano-Frankivsk National Medical University, Ivano-Frankivsk (A.K.) - all in Ukraine; the Russian Scientific Center of Roentgen Radiology (R.G.), Central Clinical Hospital with Outpatient Clinic (D.N.), and Hertzen Moscow Cancer Research Institute (B.A.), Moscow; the Christie NHS Foundation Trust, Manchester (R.H.), and Barts Health and the Royal Free NHS Trusts, Barts Cancer Institute, and Queen Mary University of London, London (T.P.) - all in the United Kingdom; Centre Hospitalier Universitaire (CHU) de Québec and Université Laval, Quebec, QC (F.P.), and CHU de Montréal, Montreal (D.S.) - both in Canada; Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic (B.M.); Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (S.J.A.); Centre Antoine Lacassagne, Université Côte d'Azur, Nice (D.B.), and Hôpitaux Universitaires de Lyon, Lyon (S. Tartas) - both in France; Military Institute of Medicine, Warsaw, Poland (C.S.); Rocky Mountain Cancer Center, Colorado Springs, CO (M.M.); Adelaide and Meath Hospital and University College Dublin, Dublin (R.S.M.); the Department of Urology, Eberhard-Karls University Tübingen, Tübingen, Germany (J.B.); Taipei Veterans General Hospital, Taipei, Taiwan (Y.-H.C.); Osaka City University Hospital, Osaka, Japan (S. Tamada); MSD China, Beijing (Q.S.); Merck, Kenilworth, NJ (R.F.P., M.C.); and Georgetown Lombardi Comprehensive Cancer Center, Washington, DC (M.B.A.).
出版信息
N Engl J Med. 2019 Mar 21;380(12):1116-1127. doi: 10.1056/NEJMoa1816714. Epub 2019 Feb 16.
BACKGROUND
The combination of pembrolizumab and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear.
METHODS
In an open-label, phase 3 trial, we randomly assigned 861 patients with previously untreated advanced clear-cell renal-cell carcinoma to receive pembrolizumab (200 mg) intravenously once every 3 weeks plus axitinib (5 mg) orally twice daily (432 patients) or sunitinib (50 mg) orally once daily for the first 4 weeks of each 6-week cycle (429 patients). The primary end points were overall survival and progression-free survival in the intention-to-treat population. The key secondary end point was the objective response rate. All reported results are from the protocol-specified first interim analysis.
RESULTS
After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% in the pembrolizumab-axitinib group and 78.3% in the sunitinib group (hazard ratio for death, 0.53; 95% confidence interval [CI], 0.38 to 0.74; P<0.0001). Median progression-free survival was 15.1 months in the pembrolizumab-axitinib group and 11.1 months in the sunitinib group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.57 to 0.84; P<0.001). The objective response rate was 59.3% (95% CI, 54.5 to 63.9) in the pembrolizumab-axitinib group and 35.7% (95% CI, 31.1 to 40.4) in the sunitinib group (P<0.001). The benefit of pembrolizumab plus axitinib was observed across the International Metastatic Renal Cell Carcinoma Database Consortium risk groups (i.e., favorable, intermediate, and poor risk) and regardless of programmed death ligand 1 expression. Grade 3 or higher adverse events of any cause occurred in 75.8% of patients in the pembrolizumab-axitinib group and in 70.6% in the sunitinib group.
CONCLUSIONS
Among patients with previously untreated advanced renal-cell carcinoma, treatment with pembrolizumab plus axitinib resulted in significantly longer overall survival and progression-free survival, as well as a higher objective response rate, than treatment with sunitinib. (Funded by Merck Sharp & Dohme; KEYNOTE-426 ClinicalTrials.gov number, NCT02853331.).
背景
在一项涉及未经治疗的晚期肾细胞癌患者的 1b 期试验中，帕博利珠单抗联合阿昔替尼显示出抗肿瘤活性。在这些患者中，帕博利珠单抗联合阿昔替尼是否会比舒尼替尼产生更好的结果尚不清楚。
方法
在一项开放标签、3 期试验中，我们将 861 名未经治疗的晚期透明细胞肾细胞癌患者随机分配接受帕博利珠单抗（200mg）每 3 周静脉注射一次加阿昔替尼（5mg）每日口服两次（432 例）或舒尼替尼（50mg）每日口服一次，每个 6 周周期的前 4 周（429 例）。主要终点是在意向治疗人群中的总生存期和无进展生存期。主要次要终点是客观缓解率。所有报告的结果均来自方案规定的第一次中期分析。
结果
中位随访 12.8 个月后，12 个月时存活的患者估计百分比为：帕博利珠单抗-阿昔替尼组为 89.9%，舒尼替尼组为 78.3%（死亡风险比，0.53；95%置信区间[CI]，0.38 至 0.74；P<0.0001）。帕博利珠单抗-阿昔替尼组无进展生存期为 15.1 个月，舒尼替尼组为 11.1 个月（疾病进展或死亡的风险比，0.69；95%CI，0.57 至 0.84；P<0.001）。帕博利珠单抗-阿昔替尼组的客观缓解率为 59.3%（95%CI，54.5 至 63.9），舒尼替尼组为 35.7%（95%CI，31.1 至 40.4）（P<0.001）。帕博利珠单抗联合阿昔替尼的获益在国际转移性肾细胞癌数据库联盟风险组（即有利、中等和不良风险）中均观察到，并且与程序性死亡配体 1 表达无关。帕博利珠单抗-阿昔替尼组有 75.8%的患者和舒尼替尼组有 70.6%的患者发生任何原因导致的 3 级或更高级别的不良事件。
结论
在未经治疗的晚期肾细胞癌患者中，与舒尼替尼相比，帕博利珠单抗联合阿昔替尼治疗可显著延长总生存期和无进展生存期，并提高客观缓解率。（由默克公司资助；KEYNOTE-426 临床试验。gov 编号，NCT02853331。）
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