KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin-Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma.

IF 5.7 2区 医学 Q1 Medicine
Cancer Science Pub Date : 2025-05-23 DOI:10.1111/cas.70082
Takashi Kijima, Terufumi Kato, Yasushi Goto, Kozo Kuribayashi, Koji Mikami, Yoshiki Negi, Shuji Murakami, Tatsuya Yoshida, Masae Homma, Akira Wakana, Kazuo Noguchi, Nobukazu Fujimoto
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引用次数: 0

Abstract

Pleural mesothelioma (PM) is an inflammatory cancer linked with asbestos exposure and has a poor prognosis. We report results of the phase 1b KEYNOTE-A17 study (NCT04153565) of first-line pembrolizumab plus chemotherapy in Japanese participants with advanced PM. Participants aged ≥ 20 years with previously untreated, histologically confirmed advanced or unresectable PM received pembrolizumab 200 mg every 3 weeks (Q3W) for ≤ 35 cycles with cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 Q3W for 4-6 cycles. Primary endpoints were the rate of dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. DLTs were assessed during cycle 1 in 18 participants, and having ≤ 8 participants with DLTs was considered tolerable. AEs were graded per NCI CTCAE 5.0. Tumor response was evaluated per modified RECIST for PM by the investigator. Among 19 participants enrolled, the median study follow-up was 30.8 (range, 27.8-33.3) months (data cutoff September 21, 2022). Of 18 participants evaluated for DLTs, 2 (11%) experienced 4 DLTs (hypoalbuminemia, malaise, pyrexia in 1 participant; uveitis in 1 participant). 18/19 participants (95%) experienced treatment-related AEs; 14 (74%) had grade 3-4 events (no grade 5). Treatment-related AEs led to discontinuation of any drug in 5 participants (26%). The objective response rate was 74% (partial response, n = 14), and the median (range) duration of response was 16.8 (3.0-26.3+) months. First-line pembrolizumab plus chemotherapy was tolerable based on the low incidence of DLTs and showed acceptable safety and preliminary antitumor activity in Japanese participants with advanced PM. Trial Registration: NCT04153565.

KEYNOTE-A17:一线派姆单抗联合顺铂-培美曲塞治疗日本晚期胸膜间皮瘤患者
胸膜间皮瘤(PM)是一种与石棉暴露有关的炎症性癌症,预后不良。我们报告1b期KEYNOTE-A17研究(NCT04153565)在日本晚期PM患者中一线派姆单抗加化疗的结果。年龄≥20岁,既往未治疗,组织学证实的晚期或不可切除的PM患者接受派姆单抗200mg / 3周(Q3W),≤35个周期,顺铂75mg /m2,培美曲塞500mg /m2, Q3W, 4-6个周期。主要终点是剂量限制性毒性(dlt)、不良事件(ae)和因ae而中断治疗的发生率。在第1周期对18名参与者进行了dlt评估,≤8名参与者的dlt被认为是可容忍的。ae按NCI CTCAE 5.0分级。研究者根据改良的RECIST评估PM的肿瘤反应。在入组的19名参与者中,中位研究随访时间为30.8(范围27.8-33.3)个月(数据截止日期为2022年9月21日)。在18名接受dlt评估的参与者中,2名(11%)经历了4种dlt(1名参与者低白蛋白血症、不适、发热;葡萄膜炎1例)。18/19的参与者(95%)经历了治疗相关的不良事件;14例(74%)发生3-4级事件(无5级事件)。治疗相关不良事件导致5名参与者(26%)停药。客观缓解率为74%(部分缓解,n = 14),中位(范围)缓解持续时间为16.8(3.0-26.3+)个月。基于低发生率的dlt,一线派姆单抗加化疗是可耐受的,并且在日本晚期PM患者中显示出可接受的安全性和初步抗肿瘤活性。试验注册:NCT04153565。
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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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