Jann N Sarkaria, Karla V Ballman, Sani H Kizilbash, Erik P Sulman, Caterina Giannini, Bret B Friday, Nicholas A Butowski, Nimish A Mohile, David E Piccioni, James D Battiste, Jan Drappatz, Jian L Campian, Sandeep Mashru, Kurt A Jaeckle, Barbara J O'Brien, Jesse G Dixon, Brian F Kabat, Nadia L Laack, Leland S Hu, Timothy Kaufmann, Priya Kumthekar, Benjamin M Ellingson, S Keith Anderson, Evanthia Galanis
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引用次数: 0
摘要
重要性：胶质母细胞瘤患者在接受手术切除、放疗、替莫唑胺和肿瘤治疗领域的标准治疗后，预后较差：基于临床前数据显示多腺苷二磷酸核糖聚合酶1/2抑制剂veliparib与替莫唑胺联用时具有显著的化疗增敏作用，评估veliparib与替莫唑胺联用治疗胶质母细胞瘤的效果：2014年12月15日至2018年12月15日期间，新确诊的胶质母细胞瘤患者伴有MGMT启动子高甲基化，且已同时完成放射治疗和替莫唑胺治疗，这些患者被纳入了这项肿瘤临床试验联盟（Alliance for Clinical Trials in Oncology）试验。本次分析的数据于2023年4月21日锁定：患者随机接受标准辅助替莫唑胺（150-200 mg/m2，口服，第1-5天）联合安慰剂或veliparib（40 mg，口服，每日2次，第1-7天）治疗6个周期.主要结局和测量指标：3期试验的主要终点是总生存期（OS）：结果：在第2期试验中，有322名患者被随机选中，另有125名患者被随机选中完成第3期试验，在最终的第3期试验分析中，共有447名患者。患者年龄的中位数（范围）为 60（20-85）岁，190 名患者（42.5%）为女性。安慰剂治疗组的中位OS为24.8个月（90% CI，22.6-27.7），veliparib治疗组为28.1个月（90% CI，24.3-33.3）（P = .17）。生存期的差异未达到预设的疗效终点。不过，在24至48个月的随访期间，生存曲线的分离有利于veliparib治疗组。试验性联合用药的耐受性良好，3级或4级血液学毒性反应的升高是可以接受的：该试验发现，在替莫唑胺辅助治疗的基础上加用veliparib并不能显著延长新诊断的MGMT超甲基化胶质母细胞瘤患者的OS：试验注册：ClinicalTrials.gov Identifier：NCT02152982。
Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Randomized Clinical Trial.
Importance: The prognosis for patients with glioblastoma is poor following standard therapy with surgical resection, radiation, temozolomide, and tumor-treating fields.
Objectives: To evaluate the combination of veliparib and temozolomide in glioblastoma based on preclinical data demonstrating significant chemosensitizing effects of the polyadenosine diphosphate-ribose polymerase 1/2 inhibitor veliparib when combined with temozolomide.
Design, setting, and participants: Patients with newly diagnosed glioblastoma with MGMT promoter hypermethylation who had completed concomitant radiation and temozolomide were enrolled between December 15, 2014, and December 15, 2018, in this Alliance for Clinical Trials in Oncology trial. The data for this analysis were locked on April 21, 2023.
Interventions: Patients were randomized and treated with standard adjuvant temozolomide (150-200 mg/m2 orally, days 1-5) combined with either placebo or veliparib (40 mg orally, twice daily, days 1-7) for 6 cycles.
Main outcomes and measures: The primary end point for the phase 3 portion of the trial was overall survival (OS).
Results: There were 322 patients randomized during the phase 2 accrual period and an additional 125 patients randomized to complete the phase 3 accrual, for a total of 447 patients in the final phase 3 analysis. The median (range) age for patients was 60 (20-85) years and 190 patients (42.5%) were female. The median OS was 24.8 months (90% CI, 22.6-27.7) for the placebo arm and 28.1 months (90% CI, 24.3-33.3) for the veliparib arm (P = .17). The difference in survival did not meet the prespecified efficacy end point. However, there was a separation of the survival curves that favored the veliparib arm over 24 to 48 months of follow-up. The experimental combination was well tolerated with an acceptable elevation in grade 3 or 4 hematologic toxic effects.
Conclusions and relevance: This trial found that adding veliparib to adjuvant temozolomide did not significantly extend OS in patients with newly diagnosed, MGMT-hypermethylated glioblastoma.
期刊介绍：
At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science.
Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers.
We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.
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