Cabozantinib联合Atezolizumab治疗晚期进展性内分泌恶性肿瘤：一项多队列、一揽子、II期试验（CABATEN/GETNE-T1914）

IF 10.2 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2025-09-12 DOI:10.1158/1078-0432.ccr-25-2143

Jaume Capdevila,Jorge Hernando,Javier Molina-Cerrillo,Marta Benavent Viñuales,Rocio Garcia-Carbonero,Alex Teulé,Ana Custodio,Paula Jimenez-Fonseca,Carlos Lopez,Cinta Hierro,Alberto Carmona-Bayonas,Vicente Alonso,Marta Llanos,Isabel Sevilla,Alejandro Garcia-Alvarez,Teresa Alonso-Gordoa,Inmaculada Gallego Jiménez,Beatriz Antón-Pascual,Andrea Modrego Sánchez,Enrique Grande

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Patients received atezolizumab 1200 mg IV Q3W plus cabozantinib 40 mg/day PO until disease progression or unacceptable toxicity. The primary objective was overall response rate (ORR) by RECIST 1.1.\r\n\r\nRESULTS\r\nFrom October 2020 to December 2022, 93 patients were included. ORR was 14.3% (95% CI:1.8-42.8) in ATC (N=14); 8.3% (95% CI:1.0-27.0) in ACC (N=24); 15.4% (95% CI:1.9-45.5) in PPGL (N=13) and 16.7% (95% CI: 4.7-37.4) in GEP-NET (N=24). LungNET and G3 EP-NEN had no responses. Duration of response (DoR) was 20.4 months in ATC; 13.1 months in ACC; 12.2 months in PPGL and 15.8 months in GEP-NET. Survival rates at 12 months in ATC and ACC were 47.6 %and 47.6 % respectively. 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引用次数: 0

摘要

背景：多激酶抑制剂（MKIs）在内分泌肿瘤中已显示出疗效，并且在其他肿瘤中已注意到与免疫检查点抑制剂（ICI）的协同作用。患者和方法：这是一项前瞻性、多中心、开放标签、Simon 2期优化设计的II期研究，包括6个队列的晚期难治内分泌和神经内分泌肿瘤患者：肺高分化神经内分泌肿瘤（lungNET）、间变性甲状腺癌（ATC）、肾上腺皮质癌（ACC）、嗜铬细胞瘤/副神经节瘤（PPGL）、高分化胃胰腺NET （GEP-NET）和3级肺外神经内分泌肿瘤（G3 EP-NEN）。患者接受atezolizumab 1200mg IV Q3W + cabozantinib 40mg /d PO，直到疾病进展或不可接受的毒性。主要目标是RECIST 1.1的总缓解率（ORR）。结果2020年10月至2022年12月，纳入93例患者。ATC的ORR为14.3% (95% CI:1.8-42.8) (N=14)；ACC患者占8.3% (95% CI:1.0-27.0) (N=24)；PPGL组（N=13） 15.4% (95% CI:1.9-45.5)， GEP-NET组（N=24） 16.7% （95% CI: 4.7-37.4）。LungNET和G3 EP-NEN无反应。ATC组反应持续时间（DoR）为20.4个月；ACC 13.1个月；PPGL组12.2个月，GEP-NET组15.8个月。ATC和ACC的12个月生存率分别为47.6%和47.6%。未观察到意外毒性。结论cabozantinib和atezolizumab在侵袭性和预处理的ACC和ATC中显示出良好的ORR和初步的长期生存率，值得进一步研究。

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Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A multi-cohort, Basket, Phase II Trial (CABATEN/GETNE-T1914).

BACKGROUND Multikinase inhibitors (MKIs) have shown efficacy in endocrine neoplasms and synergism with immune-checkpoint inhibitors (ICI) has been noted in other tumors. PATIENTS AND METHODS This is a prospective, multi-center, open-label, Simon 2 stage optimal design, phase II study including patients with advanced and refractory endocrine and neuroendocrine neoplasms in 6 cohorts: lung well-differentiated neuroendocrine tumors (lungNET), anaplastic thyroid cancer (ATC), adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PPGL), well-differentiated gastroenteropancreatic NET (GEP-NET), and grade 3 extrapulmonary neuroendocrine neoplasms (G3 EP-NEN). Patients received atezolizumab 1200 mg IV Q3W plus cabozantinib 40 mg/day PO until disease progression or unacceptable toxicity. The primary objective was overall response rate (ORR) by RECIST 1.1. RESULTS From October 2020 to December 2022, 93 patients were included. ORR was 14.3% (95% CI:1.8-42.8) in ATC (N=14); 8.3% (95% CI:1.0-27.0) in ACC (N=24); 15.4% (95% CI:1.9-45.5) in PPGL (N=13) and 16.7% (95% CI: 4.7-37.4) in GEP-NET (N=24). LungNET and G3 EP-NEN had no responses. Duration of response (DoR) was 20.4 months in ATC; 13.1 months in ACC; 12.2 months in PPGL and 15.8 months in GEP-NET. Survival rates at 12 months in ATC and ACC were 47.6 %and 47.6 % respectively. No unexpected toxicity was observed. CONCLUSION Cabozantinib and atezolizumab were safely administered and showed promising ORR and preliminary long-term survival rates were observed in aggressive and pretreated ACC and ATC, which warrants further investigation.

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来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.