尼伐单抗联合来伐替尼治疗晚期胆道癌的 I/II 期研究（JCOG1808/NCCH1817，SNIPE）

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-10-01 DOI:10.1016/j.esmoop.2024.103919

M. Ueno , C. Morizane , M. Ikeda , M. Ozaka , F. Nagashima , T. Kataoka , J. Mizusawa , A. Ohba , S. Kobayashi , H. Imaoka , A. Kasuga , N. Okano , Y. Nagasaka , M. Sasaki , J. Furuse , T. Okusaka

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引用次数: 0

摘要

背景虽然顺铂加吉西他滨和其他联合疗法改善了晚期胆道癌（BTC）的生存率，但仍有大量医疗需求未得到满足。本研究旨在评估尼伐单抗联合来伐替尼用于晚期胆道癌二线治疗的有效性和安全性。患者和方法尼伐单抗（240 毫克）每两周给药一次。I期确定了来伐替尼的II期推荐剂量（20毫克或14毫克）。在II期，主要终点是客观反应率（ORR）。次要终点是疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和安全性。计划样本量为32例患者，功率为80%，单侧α误差为5%，阈值ORR为10%，预期ORR为30%。结果在I期，6例患者的来伐替尼推荐剂量被确定为20毫克，出现了一种剂量限制性毒性（心肌炎）。在II期，我们共招募了26名患者。ORR、DCR、中位OS和PFS分别为9.4%[90%置信区间（CI）为2.6%至22.5%]、53.1%（95% CI为34.7%至70.9%）、6.4个月（95% CI为4.9至9.7个月）和2.5个月（95% CI为1.5至4.1个月）。使用抗生素的患者未观察到任何反应。3级或4级不良反应为高血压（59.4%）和胆道感染（37.5%）。结论Nivolumab联合lenvatinib治疗晚期BTC具有可控的安全性，但在二线治疗中的疗效有限。

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Phase I/II study of nivolumab plus lenvatinib for advanced biliary tract cancer (JCOG1808/NCCH1817, SNIPE)

Background

Although cisplatin plus gemcitabine and other combinations have improved the survival of advanced biliary tract cancer (BTC), high unmet medical needs remain. This study aimed to assess the efficacy and safety of nivolumab plus lenvatinib in the second-line treatment for advanced BTC.

Patients and methods

Nivolumab (240 mg) was administered biweekly. Phase I determined the recommended phase II dose of lenvatinib (20 mg or 14 mg). In phase II, the primary endpoint was the objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The planned sample size was 32 patients with a power of 80%, a one-sided alpha error of 5%, threshold ORR of 10%, and expected ORR of 30%.

Results

In phase I, the recommended dose of lenvatinib was determined to be 20 mg in six patients, with one dose-limiting toxicity (myocarditis). In phase II, we enrolled 26 patients. ORR, DCR, and median OS and PFS were 9.4% [90% confidence interval (CI) 2.6% to 22.5%], 53.1% (95% CI 34.7% to 70.9%), and 6.4 months (95% CI 4.9-9.7 months) and 2.5 months (95% CI 1.5-4.1 months), respectively. No response was observed in patients with the usage of antibiotics. The grade 3 or 4 adverse events were hypertension (59.4%) and biliary tract infection (37.5%). Rash (28.1%) and hypothyroidism (21.9%) were observed as immune-mediated adverse events of any grade.

Conclusions

Nivolumab plus lenvatinib had a manageable safety in advanced BTC, but its efficacy in the second-line treatment was limited.

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.