Graham Jeffrey, Vogel Arndt, Cheng Ann-Lii, Bjarnason Georg A, Neal Joel W
University of Manitoba, Winnipeg, MB, Canada; CancerCare Manitoba Research Institute, CancerCare Manitoba, Winnipeg, MB, Canada.
Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Cancer Treat Rev. 2022 Nov;110:102453. doi: 10.1016/j.ctrv.2022.102453. Epub 2022 Aug 10.
We conducted a systematic literature review to identify evidence for cabozantinib activity in patients with solid tumors after prior checkpoint inhibitor (CPI) therapy.
The review was conducted according to PRISMA guidelines and registered with PROSPERO (CRD42021259873). MEDLINE®, Embase, and the Cochrane Library were searched on 19 May 2021 to identify publications reporting the efficacy/effectiveness and safety/tolerability of cabozantinib in patients with solid tumors who had received prior CPI-based therapy. Publications were screened by one reviewer with uncertainties resolved by a second and/or the full author group. Risk of bias was assessed using Gradingof Recommendations Assessment, Development and Evaluation (GRADE) for clinical trials and the Newcastle-Ottawa Scale (NOS) for observational studies.
Of 669 publications screened, 21 were eligible: 18 reported data on renal cell carcinoma, and one each for hepatocellular carcinoma, metastatic urothelial carcinoma, and non-small cell lung cancer. Of six trial publications, three reported moderate-quality evidence and three low-quality evidence. Of 15 observational studies, NOS scores ranged from 3 to 6, suggesting a high potential for uncertainty. The studies consistently reported clinical activity for cabozantinib after CPI therapy, across treatment lines and tumor types, with no new safety signals. The findings were limited by the quality and quantity of available data.
Cabozantinib appears to have anti-tumor activity after prior CPI therapy in patients with solid tumors. Our results are driven largely by studies in renal cell carcinoma. Evidence from ongoing phase 3 trials is required to establish further the role of cabozantinib after CPI therapy.
我们进行了一项系统的文献综述,以确定卡博替尼在先前接受过检查点抑制剂(CPI)治疗的实体瘤患者中的活性证据。
该综述按照PRISMA指南进行,并在PROSPERO(CRD42021259873)上注册。于2021年5月19日检索了MEDLINE®、Embase和Cochrane图书馆,以识别报告卡博替尼在接受过基于CPI的先前治疗的实体瘤患者中的疗效/有效性以及安全性/耐受性的出版物。由一名审阅者进行筛选,不确定性由第二名审阅者和/或整个作者团队解决。使用推荐分级评估、发展和评价(GRADE)对临床试验进行偏倚风险评估,对观察性研究使用纽卡斯尔-渥太华量表(NOS)。
在筛选的669篇出版物中,21篇符合条件:18篇报告了肾细胞癌的数据,肝细胞癌、转移性尿路上皮癌和非小细胞肺癌各1篇。在6篇试验性出版物中,3篇报告了中等质量的证据,3篇报告了低质量的证据。在15项观察性研究中,NOS评分范围为3至6,表明存在高度不确定性。这些研究一致报告了卡博替尼在CPI治疗后在不同治疗线和肿瘤类型中的临床活性,且无新的安全信号。研究结果受到现有数据质量和数量的限制。
卡博替尼在先前接受过CPI治疗的实体瘤患者中似乎具有抗肿瘤活性。我们的结果主要由肾细胞癌的研究推动。需要正在进行的3期试验的证据来进一步确定卡博替尼在CPI治疗后的作用。