Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study

IF 8.6 1区医学 Q1 DERMATOLOGY

American Journal of Clinical Dermatology Pub Date : 2024-10-08 DOI:10.1007/s40257-024-00885-w

Laurent Mortier, Lisa Villabona, Ben Lawrence, Ana Arance, Marcus O. Butler, Marie Beylot-Barry, Philippe Saiag, Mahtab Samimi, Paolo A. Ascierto, Francesca Spada, Michel De Pontville, Michele Maio, Alfonso Berrocal, Enrique Espinosa, Jaume Capdevila, Max Levin, Debasmita Das, Clemens Krepler, Dmitri Grebennik, Vanna Chiarion-Sileni

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引用次数: 0

Abstract

Background

The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC).

Objective

The aim was to report results from the primary analysis of KEYNOTE-913.

Patients and Methods

Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200 mg intravenously every 3 weeks for up to 35 treatments (~ 2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability.

Results

Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7–59.4). The ORR was 49% (95% confidence interval [CI] 35–63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8–52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3–26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3–5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome.

Conclusions

Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population.

Trial Registration

Clinicaltrials.gov, NCT03783078.

查看原文本刊更多论文

Pembrolizumab 用于复发性局部晚期或转移性梅克尔细胞癌的一线治疗：单臂、开放标签、III 期 KEYNOTE-913 研究结果。

研究背景III期KEYNOTE-913研究旨在评估pembrolizumab作为晚期梅克尔细胞癌（MCC）患者一线疗法的有效性和安全性：目的：报告KEYNOTE-913的主要分析结果：复发性局部晚期或转移性 MCC 患者接受 pembrolizumab 200 mg 静脉注射，每 3 周一次，最多治疗 35 次（约 2 年）。主要终点是根据实体瘤反应评估标准 1.1 版（RECIST v1.1）通过盲法独立中央审查（BICR）得出的客观反应率（ORR）。次要终点是BICR根据RECIST v1.1标准得出的反应持续时间（DOR）和无进展生存期（PFS）、总生存期（OS）以及安全性和耐受性：55名患者接受了pembrolizumab治疗。从首次给药到数据截止（2024 年 2 月 15 日）的中位时间为 50.3 个月（38.7-59.4 个月）。ORR为49%（95%置信区间[CI] 35-63），其中12例完全应答，15例部分应答。中位DOR为39.8个月（范围4.8-52.5+），24个月的DOR率为69%。中位 PFS 为 9.3 个月（95% CI 3-26），24 个月的 PFS 率为 39%。中位OS为24.3个月（95% CI 12.4至未达到），24个月OS率为51%。38名患者（69%）发生了任何等级的治疗相关不良事件（AEs）；13名患者（24%）发生了3-5级AEs。最常见的治疗相关不良反应是疲劳（12 例 [22%]）、瘙痒（12 例 [22%]）和脂肪酶升高（10 例 [18%]）。一名患者死于治疗相关的格林-巴利综合征：Pembrolizumab为复发性局部晚期或转移性MCC患者提供了持久的抗肿瘤活性和良好的生存期，并具有可控的安全性，支持在这一人群中使用：试验注册：Clinicaltrials.gov，NCT03783078。

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来源期刊

American Journal of Clinical Dermatology 医学-皮肤病学

CiteScore

15.20

自引率

2.70%

发文量

审稿时长

>12 weeks

期刊介绍： The American Journal of Clinical Dermatology is dedicated to evidence-based therapy and effective patient management in dermatology. It publishes critical review articles and clinically focused original research covering comprehensive aspects of dermatological conditions. The journal enhances visibility and educational value through features like Key Points summaries, plain language summaries, and various digital elements, ensuring accessibility and depth for a diverse readership.