From Memorial Sloan Kettering Cancer Center, New York (I.K.M.); the Brain Tumor Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands (M.J.B.); Tel Aviv Medical Center, Tel Aviv University, Tel Aviv (D.T.B., S.Y.-K.), and the Davidoff Cancer Center, Rabin Medical Center, Petah Tikva (S.Y.-K.) - both in Israel; Sorbonne Université, Institut du Cerveau, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires la Pitié Salpêtrière-Charles Foix, Paris (M.T.), and Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon (F.D.) - both in France; Duke University Medical Center, Durham, NC (K.B.P.); the University of California, San Francisco, San Francisco (J.C.); Huntsman Cancer Institute, University of Utah, Salt Lake City (J.M.); the Royal Marsden Hospital, London (L.W.); Princess Margaret Cancer Centre (W.P.M.), and Sunnybrook Health Sciences Centre (J.R.P.), University of Toronto (W.P.M.) - both in Toronto; the University of Michigan Comprehensive Cancer Center, Ann Arbor (Y.U.); the University of Alabama at Birmingham, Birmingham (B.N.); Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore (M.H.); Lundin Family Brain Tumor Research Center, University Hospital of Lausanne, and the University of Lausanne - both in Lausanne, Switzerland (A.F.H.); Kyoto University Graduate School of Medicine, Kyoto, Japan (Y.A.); Hospital Universitario 12 de Octubre, Madrid (J.M.S.); Universitätsklinikum Heidelberg and the German Cancer Research Center - both in Heidelberg, Germany (W.W.); the University of Turin, Turin, Italy (R.S.); Ohio State University Wexner Medical Center, Columbus (P.G.); Sylvester Comprehensive Cancer Center and the Department of Neurology, University of Miami, Miami (M.F.); University of Texas Southwestern Medical Center, Dallas (E.A.M.); Servier Pharmaceuticals (S.S., D.Z., S.S.P., L.S., I.H.) and Dana-Farber Cancer Institute (P.Y.W.) - both in Boston; and the University of California, Los Angeles, Los Angeles (T.F.C.).
N Engl J Med. 2023 Aug 17;389(7):589-601. doi: 10.1056/NEJMoa2304194. Epub 2023 Jun 4.
BACKGROUND: Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumors that cause considerable disability and premature death. Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas. METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles. The primary end point was imaging-based progression-free survival according to blinded assessment by an independent review committee. The key secondary end point was the time to the next anticancer intervention. Crossover to vorasidenib from placebo was permitted on confirmation of imaging-based disease progression. Safety was also assessed. RESULTS: A total of 331 patients were assigned to receive vorasidenib (168 patients) or placebo (163 patients). At a median follow-up of 14.2 months, 226 patients (68.3%) were continuing to receive vorasidenib or placebo. Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.1 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.27 to 0.56; P<0.001). The time to the next intervention was significantly improved in the vorasidenib group as compared with the placebo group (hazard ratio, 0.26; 95% CI, 0.15 to 0.43; P<0.001). Adverse events of grade 3 or higher occurred in 22.8% of the patients who received vorasidenib and in 13.5% of those who received placebo. An increased alanine aminotransferase level of grade 3 or higher occurred in 9.6% of the patients who received vorasidenib and in no patients who received placebo. CONCLUSIONS: In patients with grade 2 IDH-mutant glioma, vorasidenib significantly improved progression-free survival and delayed the time to the next intervention. (Funded by Servier; INDIGO ClinicalTrials.gov number, NCT04164901.).
背景：异柠檬酸脱氢酶（IDH）突变型 2 级胶质瘤是导致严重残疾和过早死亡的恶性脑肿瘤。口服脑穿透性突变 IDH1 和 IDH2 酶抑制剂沃拉西尼在 IDH 突变型胶质瘤中显示出初步疗效。
方法：在一项双盲、3 期临床试验中，我们将未经手术以外的其他治疗（包括手术）的残留或复发的 2 级 IDH 突变型胶质瘤患者随机分为接受口服沃拉西尼（40mg 每日 1 次）或匹配安慰剂的 28 天周期。主要终点是独立审查委员会盲法评估的基于影像学的无进展生存期。关键次要终点是下一次抗癌干预的时间。在确认基于影像学的疾病进展后，允许从安慰剂交叉到沃拉西尼。还评估了安全性。
结果：共有 331 名患者被分配接受沃拉西尼（168 名患者）或安慰剂（163 名患者）。中位随访 14.2 个月时，226 名患者（68.3%）继续接受沃拉西尼或安慰剂治疗。与安慰剂组相比，沃拉西尼组的无进展生存期显著改善（中位无进展生存期，27.7 个月比 11.1 个月；疾病进展或死亡的风险比为 0.39；95%置信区间[CI]，0.27 至 0.56；P<0.001）。与安慰剂组相比，沃拉西尼组的下一次干预时间显著改善（风险比，0.26；95%CI，0.15 至 0.43；P<0.001）。接受沃拉西尼治疗的患者中有 22.8%发生 3 级或更高级别的不良反应，而接受安慰剂治疗的患者中有 13.5%发生不良反应。接受沃拉西尼治疗的患者中有 9.6%发生 3 级或更高级别的丙氨酸氨基转移酶升高，而接受安慰剂治疗的患者中无丙氨酸氨基转移酶升高。
结论：在 2 级 IDH 突变型胶质瘤患者中，沃拉西尼显著改善了无进展生存期，并延迟了下一次干预的时间。（由 Servier 资助；INDIGO ClinicalTrials.gov 编号，NCT04164901。）
N Engl J Med. 2023-8-17
Cochrane Database Syst Rev. 2017-7-26
Neuro Oncol. 2024-12-25
Cochrane Database Syst Rev. 2018-2-6
Cochrane Database Syst Rev. 2022-9-26
Cochrane Database Syst Rev. 2005-7-20
N Engl J Med. 2023-6-8
Eur J Nucl Med Mol Imaging. 2025-9-10
Pharmacoecon Open. 2025-9-6
Biomed Rep. 2025-8-19
Neurooncol Adv. 2025-8-20
Neurosci Bull. 2025-8-28
Cancers (Basel). 2025-8-15
Cancers (Basel). 2025-8-12
Neuro Oncol. 2021-8-2
Nat Rev Clin Oncol. 2021-3
Zotero 插件