Li Daneng, Loriot Yohann, Burgoyne Adam M, Cleary James M, Santoro Armando, Lin Daniel, Aix Santiago Ponce, Garrido-Laguna Ignacio, Sudhagoni Ramu, Guo Xiang, Andrianova Svetlana, Paulson Scott
City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Department of Cancer Medicine, Gustave Roussy Institute, INSERM 981, University Paris-Saclay, Villejuif, France.
EClinicalMedicine. 2023 Dec 21;67:102376. doi: 10.1016/j.eclinm.2023.102376. eCollection 2024 Jan.
Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ.
COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, metastatic, or recurrent disease per RECIST version 1.1. Patients received oral cabozantinib 40 mg daily and intravenous atezolizumab 1200 mg once every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate per RECIST version 1.1.
Patients were screened between February 14, 2019, and May 7, 2020, and 61 (30 aHCC, 31 GC/GEJ) were enrolled and received at least one dose of study treatment. Median duration of follow-up was 31.2 months (IQR 28.5-32.7) for aHCC and 30.4 months (28.7-31.9) for GC/GEJ. Objective response rate was 13% (4/30, 95% CI 4-31) for aHCC and 0% (95% CI 0-11) for GC/GEJ. Six (20%) aHCC patients and three (10%) GC/GEJ patients had treatment-related adverse events resulting in discontinuation of either study drug.
Cabozantinib plus atezolizumab had clinical activity with a manageable safety profile in aHCC previously untreated with systemic anticancer therapy. Clinical activity of cabozantinib plus atezolizumab was minimal in previously treated GC/GEJ.
Exelixis, Inc., Alameda, CA, USA.
卡博替尼已被批准用于既往接受过治疗的晚期肝细胞癌（aHCC），并已在胃癌（GC）和胃食管交界腺癌（GEJ）中进行了研究。阿替利珠单抗联合贝伐单抗已被批准用于既往未接受过全身治疗的不可切除或转移性HCC。我们评估了卡博替尼联合阿替利珠单抗在既往未接受过全身抗癌治疗或既往接受过治疗的GC/GEJ的aHCC中的疗效和安全性。
COSMIC-021（ClinicalTrials.gov，NCT03170960）是一项针对实体瘤的开放标签1b期研究，包括剂量爬坡阶段，随后是肿瘤特异性扩展队列，包括aHCC（队列14）和GC/GEJ（队列15）。符合条件的患者年龄≥18岁，根据RECIST 1.1版有可测量的局部晚期、转移性或复发性疾病。患者接受每日口服卡博替尼40mg和每3周静脉注射阿替利珠单抗1200mg，直至疾病进展或出现不可接受的毒性。主要终点是研究者根据RECIST 1.1版评估的客观缓解率。
在2019年2月14日至2020年5月7日期间对患者进行了筛选，61例（30例aHCC，31例GC/GEJ）入组并接受了至少一剂研究治疗。aHCC的中位随访时间为31.2个月（IQR 28.5-32.7），GC/GEJ为30.4个月（28.7-31.9）。aHCC的客观缓解率为13%（4/30，95%CI 4-31），GC/GEJ为0%（95%CI 0-11）。6例（20%）aHCC患者和3例（10%）GC/GEJ患者发生了与治疗相关的不良事件，导致停用任何一种研究药物。
卡博替尼联合阿替利珠单抗在既往未接受过全身抗癌治疗的aHCC中具有临床活性，安全性可控。卡博替尼联合阿替利珠单抗在既往接受过治疗的GC/GEJ中的临床活性极小。
美国加利福尼亚州阿拉米达的Exelixis公司。
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