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).

IF 4.3 2区医学 Q2 ONCOLOGY Therapeutic Advances in Medical Oncology Pub Date : 2024-09-28 eCollection Date: 2024-01-01 DOI:10.1177/17588359241277656

Annika Auranen, Matthew A Powell, Vladyslav Sukhin, Lisa M Landrum, Graziana Ronzino, Joseph Buscema, Dirk Bauerschlag, Roy Lalisang, David Bender, Lucy Gilbert, Amy Armstrong, Tamar Safra, Nicole Nevadunsky, Alexandra Sebastianelli, Brian Slomovitz, Kari Ring, Robert Coleman, Iwona Podzielinski, Ashley Stuckey, Michael Teneriello, Sarah Gill, Bhavana Pothuri, Lyndsay Willmott, Sudarshan Sharma, Christine Dabrowski, Grace Antony, Shadi Stevens, Mansoor Raza Mirza, Evelyn Fleming

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Abstract

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.

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在一项III期随机安慰剂对照试验（ENGOT-EN6-NSGO/GOG-3031/RUBY）中，多司他利单抗与化疗联合治疗原发性晚期或复发性子宫内膜癌患者的安全性。

研究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）第一部分中，与单用卡铂-紫杉醇（CP）相比，多司他单抗联合卡铂-紫杉醇（CP）可显著改善无进展生存期和总生存期。在这种情况下，免疫疗法联合化疗的安全性数据有限：本分析旨在确定治疗相关不良事件（TRAE）和免疫相关不良事件（irAE）的发生情况，并描述RUBY试验第一部分中irAE的处理情况：RUBY是一项III期随机、双盲、多中心研究，在原发性晚期或复发性EC患者中，多斯他利单抗联合CP与单用CP进行比较：患者按1:1的比例随机接受多斯他利单抗500毫克或安慰剂加CP治疗，每3周1次，共6个周期；随后接受多斯他利单抗1000毫克或安慰剂治疗，每6周1次，共3年。不良事件（AEs）根据《不良事件通用术语标准》4.03版进行评估：安全人群包括487名接受了⩾1个剂量治疗的患者（241名多司他（dostarlimab）加CP；246名安慰剂加CP）。两组100%的患者都出现了治疗突发AEs。97.9%的多司他（dostarlimab）治疗组和98.8%的安慰剂治疗组患者发生了TRAE。58.5%的多斯他利单抗治疗组患者和37.0%的安慰剂治疗组患者发生了IrAEs。多斯他利单抗治疗组40.7%的患者和安慰剂治疗组16.3%的患者发生了多斯他利单抗或安慰剂相关的非器质性损伤：结论：多司他利单抗联合CP的安全性与单个成分的安全性基本一致。多斯他利单抗联合CP具有良好的收益风险特征，是治疗原发性晚期或复发性EC患者的新标准：试验注册：NCT03981796。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutic Advances in Medical Oncology ONCOLOGY-

CiteScore

8.20

自引率

2.00%

发文量

160

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Medical Oncology is an open access, peer-reviewed journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of cancer. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in medical oncology, providing a forum in print and online for publishing the highest quality articles in this area. This journal is a member of the Committee on Publication Ethics (COPE).