在一项III期、随机、安慰剂对照试验（ENGOT-EN6-NSGO/GOG-3031/RUBY）中，多斯塔利单抗联合化疗用于原发性晚期或复发性子宫内膜癌患者的安全性。
Safety of dostarlimab in combination with chemotherapy in patients with primary advanced or recurrent endometrial cancer in a phase III, randomized, placebo-controlled trial (ENGOT-EN6-NSGO/GOG-3031/RUBY).
作者信息
Auranen Annika, Powell Matthew A, Sukhin Vladyslav, Landrum Lisa M, Ronzino Graziana, Buscema Joseph, Bauerschlag Dirk, Lalisang Roy, Bender David, Gilbert Lucy, Armstrong Amy, Safra Tamar, Nevadunsky Nicole, Sebastianelli Alexandra, Slomovitz Brian, Ring Kari, Coleman Robert, Podzielinski Iwona, Stuckey Ashley, Teneriello Michael, Gill Sarah, Pothuri Bhavana, Willmott Lyndsay, Sharma Sudarshan, Dabrowski Christine, Antony Grace, Stevens Shadi, Mirza Mansoor Raza, Fleming Evelyn
机构信息
Tays Cancer Centre and FICAN Mid, Tampere University and Tampere University Hospital, Pirkanmaa Hospital District, FM3 2.krs. Biokatu 10, Tampere 33900, Finland.
National Cancer Institute Sponsored NRG Oncology, Washington University School of Medicine, St Louis, MO, USA.
出版信息
Ther Adv Med Oncol. 2024 Sep 28;16:17588359241277656. doi: 10.1177/17588359241277656. eCollection 2024.
BACKGROUND
In Part 1 of the phase III RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (EC), dostarlimab plus carboplatin-paclitaxel (CP) significantly improved progression-free survival and overall survival compared with CP alone. Limited safety data have been reported for the combination of immunotherapies plus chemotherapy in this setting.
OBJECTIVES
The objective of this analysis was to identify the occurrence of treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) and to describe irAE management in Part 1 of the RUBY trial.
DESIGN
RUBY is a phase III, randomized, double-blind, multicenter study of dostarlimab plus CP compared with CP alone in patients with primary advanced or recurrent EC.
METHODS
Patients were randomized 1:1 to dostarlimab 500 mg, or placebo, plus CP every 3 weeks for 6 cycles, followed by dostarlimab 1000 mg, or placebo, every 6 weeks for up to 3 years. Adverse events (AEs) were assessed according to Common Terminology Criteria for Adverse Events, version 4.03.
RESULTS
The safety population included 487 patients who received ⩾1 dose of treatment (241 dostarlimab plus CP; 246 placebo plus CP). Treatment-emergent AEs were experienced by 100% of patients in both arms. TRAEs occurred in 97.9% of the dostarlimab arm and 98.8% of the placebo arm.The most common TRAEs occurred at similar rates between arms and were mostly low grade. IrAEs occurred in 58.5% of patients in the dostarlimab arm and 37.0% of patients in the placebo arm. Dostarlimab- or placebo-related irAEs were reported in 40.7% of patients in the dostarlimab arm and 16.3% of the placebo arm.
CONCLUSION
The safety profile of dostarlimab plus CP was generally consistent with that of the individual components. Dostarlimab plus CP has a favorable benefit-risk profile and is a new standard of care for patients with primary advanced or recurrent EC.
TRIAL REGISTRATION
NCT03981796.
背景
在针对原发性晚期或复发性子宫内膜癌（EC）患者的III期RUBY试验（NCT03981796）的第1部分中，与单纯使用卡铂-紫杉醇（CP）相比，多斯塔利单抗联合卡铂-紫杉醇（CP）显著改善了无进展生存期和总生存期。在这种情况下，关于免疫疗法联合化疗的安全性数据有限。
目的
本分析的目的是确定治疗相关不良事件（TRAEs）和免疫相关不良事件（irAEs）的发生情况，并描述RUBY试验第1部分中irAE的管理。
设计
RUBY是一项III期、随机、双盲、多中心研究，比较多斯塔利单抗联合CP与单纯CP用于原发性晚期或复发性EC患者的疗效。
方法
患者按1:1随机分组，每3周接受一次多斯塔利单抗500mg或安慰剂加CP，共6个周期，随后每6周接受一次多斯塔利单抗1000mg或安慰剂，持续长达3年。根据不良事件通用术语标准4.03版评估不良事件（AE）。
结果
安全人群包括487例接受≥1剂治疗的患者（241例多斯塔利单抗联合CP；246例安慰剂联合CP）。两组患者均出现治疗中出现的AE。多斯塔利单抗组97.9%的患者和安慰剂组98.8%的患者发生TRAEs。两组中最常见的TRAEs发生率相似，且大多为低级别。多斯塔利单抗组58.5%的患者和安慰剂组37.0%的患者发生irAEs。多斯塔利单抗组40.7%的患者和安慰剂组16.3%的患者报告了与多斯塔利单抗或安慰剂相关的irAEs。
结论
多斯塔利单抗联合CP的安全性概况总体上与各组分一致。多斯塔利单抗联合CP具有良好的获益风险比，是原发性晚期或复发性EC患者的一种新的标准治疗方案。
试验注册号
NCT03981796。
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