舒法替尼治疗晚期神经内分泌肿瘤：两项随机、双盲、安慰剂对照的3期研究（SANET-ep和SANET-p）的最终总生存期

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-03-30 DOI:10.1016/j.ejca.2025.115398

Jianming Xu , Lin Shen , Jie Li , Zhiwei Zhou , Chunmei Bai , Zhiping Li , Yihebali Chi , Enxiao Li , Xianjun Yu , Nong Xu , Yuxian Bai , Xiuwen Wang , Xianglin Yuan , Tianshu Liu , Yongmei Yin , Jia Chen , Hanguang Hu , Xingya Li , Dianrong Xiu , Tao Zhang , Weiguo Su

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引用次数: 0

摘要

背景：sanet -ep （NCT02588170）和SANET-p （NCT02589821）在晚期胰腺外和胰腺神经内分泌肿瘤（NETs）患者中证明了与安慰剂相比，舒法替尼的有效性和安全性。在这里，我们对两项随机3期研究的最终总生存期（OS）进行了汇总分析。SANET研究是在中国进行的随机、安慰剂对照、双盲、3期研究，比较口服300 mg舒法替尼（n = 265）与安慰剂（n = 133）在不可切除/转移性、高分化NETs（1/2级）患者中的疗效和安全性。在疾病进展或研究解盲后，接受安慰剂的患者交叉/切换到开放标签的舒法替尼。通过汇总两项研究的数据，在意向治疗人群中使用Kaplan-Meier方法和Cox比例风险模型完成OS分析。采用不同的模型进行探索性分析，以纠正交叉引入的混淆效应。评估长期安全性。结果在研究结束时，69%的安慰剂组已经切换到舒法替尼。初始使用舒法替尼的患者和初始使用安慰剂的患者的中位OS分别为50.1和46.8个月(分层风险比[HR] 0.935, 95%可信区间[CI] 0.684-1.278； = 0.6727页)。校正交叉/切换引入的混杂效应后，HR范围为0.558 ~ 0.825。通常（≥10%）报告的治疗相关不良事件（3/4级）包括高血压和蛋白尿。结论：与最初使用安慰剂的患者相比，最初使用舒法替尼的患者的生存期并没有明显延长，这可能是由于从安慰剂到舒法替尼的大量交叉。没有观察到新的安全信号。临床试验注册sanet -ep （NCT02588170）和SANET-p （NCT02589821）

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Surufatinib in advanced neuroendocrine tumours: Final overall survival from two randomised, double-blind, placebo-controlled phase 3 studies (SANET-ep and SANET-p)

Background

SANET-ep (NCT02588170) and SANET-p (NCT02589821) demonstrated the efficacy and safety of surufatinib versus placebo in patients with advanced extra-pancreatic and pancreatic neuroendocrine tumours (NETs). Here, we present a pooled analysis of final overall survival (OS) from two randomised phase 3 studies.

Methods

The SANET studies were randomised, placebo-controlled, double-blind, phase 3 studies in China, comparing the efficacy and safety of oral 300-mg surufatinib (n = 265) versus placebo (n = 133) in patients with unresectable/metastatic, well-differentiated NETs (grade 1/2). After progression of disease or study unblinding, patients receiving placebo crossed over/switched to open-label surufatinib. By pooling the data from the two studies, OS analysis was completed using Kaplan–Meier methodology and a Cox proportional hazards model in the intention-to-treat population. Exploratory analyses were performed using different models to correct the confounding effect introduced by crossover. Long-term safety was assessed.

Results

At study termination, 69 % of the placebo group had crossed over/switched to surufatinib. Median OS was 50.1 versus 46.8 months for patients initially on surufatinib versus those initially on placebo (stratified hazard ratio [HR] 0.935, 95 % confidence interval [CI] 0.684–1.278; p = 0.6727). After correcting the confounding effect introduced by crossover/switching, the HR ranged from 0.558 to 0.825. Commonly (≥10 %) reported treatment-related adverse events (grade 3/4) included hypertension and proteinuria.

Conclusion

OS of patients initially on surufatinib was not significantly longer versus patients initially on placebo, likely due to the high amount of crossover from placebo to surufatinib. No new safety signals were observed.

Clinical trials registration

SANET-ep (NCT02588170) and SANET-p (NCT02589821)

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.