本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(24)00317-9

摘要内容如下：

背景

Pembrolizumab已显示出对持续性、复发性或转移性宫颈癌的疗效。免疫治疗可增强放化疗的效果。在该3期临床试验中，我们评估了局部晚期宫颈癌放化疗中加入pembrolizumab的疗效和安全性。

方法

在这项随机、双盲、安慰剂对照的3期ENGOT-CX11/Gog-3047/KEYNOTE-A18临床试验中，来自30个国家176个医疗中心的新诊断的高危局部晚期宫颈癌患者（年龄≥18岁）被随机分配（1:1）接受5个周期的pembrolizumab（200 mg）或安慰剂，每3周一次，外加放化疗。然后每6周服用15个周期的Pembrolizumab（400 mg）或安慰剂。根据计划的体外放射治疗类型（调强放射治疗或容积调节ARC治疗vs非调强放射治疗或非容积调节ARC治疗）、筛查时的宫颈癌分期（国际妇产科联合会2014年IB2-IIb期淋巴结阳性vs III-IVa期）和计划的总放射治疗（体外放射治疗加近距离放射治疗）剂量（<70 Gy vs≥70 Gy等效剂量，2 Gy分次）进行随机化分层。主要终点是无进展生存期，根据实体瘤1.1版的疗效评价标准，由研究者或组织病理学确认可疑疾病进展和总生存期。初步分析在意向治疗人群中进行，包括所有随机分配的参与者。在治疗人群中评估安全性，包括所有随机分配的接受至少一剂研究治疗的患者。该研究在ClinicalTrials.gov，NCT04221945上注册，不对新参与者开放。

调查结果

在2020年6月9日至2022年12月15日期间，1060名参与者被随机分配接受治疗，其中529人被分配到Pembrolizumab-放化疗组，531人被分配到安慰剂-放化疗组。在数据截止日（2023年1月9日），两个治疗组的中位随访时间为17.9个月（IQR 11.3-22.3）。两组均未达到中位无进展生存期；在24个月时，Pembrolizumab-放化疗组的发生率为68%，而安慰剂-放化疗组为57%。疾病进展或死亡的风险比（HR）为0.70（95%CI 0.55-0.89，P=0.0020），符合方案规定的主要目标。Pembrolizumab-放化疗组24个月总生存率为87%，安慰剂-放化疗组为81%（信息分数42.9%）。死亡HR为0.73（0.49~1.07）；这些数据还没有越过统计学意义的界限。3级或更高级别的不良事件发生率在pembrolizumab-放化疗组为75%，在安慰剂-放化疗组为69%。

解释

Pembrolizumab联合放化疗显著改善了新诊断的高危局部晚期宫颈癌患者的无进展生存期。

英文原文如下：

Abstracts

BACKGROUND  Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer.

METHODS  In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants.

FINDINGS  Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group.

INTERPRETATION  Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer.

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