Hayes Aimee R, Chan David L H, Chan Bryan A, Pavlakis Nick
Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK.
The University of Sydney, Camperdown, NSW, Australia.
J Neuroendocrinol. 2021 Sep;33(9):e13015. doi: 10.1111/jne.13015. Epub 2021 Aug 16.
The quality and reporting of neuroendocrine tumour (NET) clinical trials has previously been found to be heterogeneous impairing trial interpretability. We aimed to perform an updated review of the quality of phase II/III clinical trials in NET to assess if trial design and reporting have improved since 2011. We performed a PubMed search for phase II/III trials evaluating systemic anticancer therapies or liver-directed therapies published between 2011 and 2018. Data collected comprised administrative data, study population characteristics, endpoints, reporting and statistical design parameters, and results. Sixty studies were included (5218 patients): 50 phase II and 10 phase III trials. Study populations were heterogeneous: 52% of trials allowed tumours from various primary sites, 28% allowed both well- and poorly-differentiated tumour morphology or did not specify, and 57% did not report proliferative indices and/or tumour grade in ≥80% of the study population. Only 36% of trials mandated radiological disease progression on participant enrolment using a validated measure. Statistical design and primary endpoint were clearly defined in 67% and 88% of trials, respectively. Toxicity (88%), radiological response rate (85%) and progression-free survival/time to progression (82%) were well reported in a majority of trials, but health-related quality of life was included in the minority. Of the randomised trials (n = 11), study populations were more homogeneous and study design was more often clearly defined; however, only 45% mandated radiological progression at baseline as measured per Response Evaluation Criteria In Solid Tumours, and reporting of health-related quality of life (55%) remained suboptimal. The design and reporting of NET clinical trials, predominantly of single-arm phase II trials, remains suboptimal and has not considerably improved over time despite the growth in our knowledge of the biology and unique characteristics of NETs. Higher quality is seen in randomised trials, although certain design and reporting elements remain inadequate in some studies. We must prioritise the design and conduct of NET clinical trials to effectively inform future research and guide practice change.
先前已发现神经内分泌肿瘤（NET）临床试验的质量和报告存在异质性，这削弱了试验的可解释性。我们旨在对NET的II/III期临床试验质量进行更新综述，以评估自2011年以来试验设计和报告是否有所改进。我们在PubMed上搜索了2011年至2018年间评估全身抗癌疗法或肝导向疗法的II/III期试验。收集的数据包括管理数据、研究人群特征、终点、报告和统计设计参数以及结果。纳入了60项研究（5218例患者）：50项II期试验和10项III期试验。研究人群具有异质性：52%的试验允许来自不同原发部位的肿瘤，28%的试验允许高分化和低分化肿瘤形态并存或未明确说明，57%的试验在≥80%的研究人群中未报告增殖指数和/或肿瘤分级。只有36%的试验在参与者入组时使用经过验证的测量方法规定了影像学疾病进展。67%和88%的试验分别明确界定了统计设计和主要终点。大多数试验对毒性（88%）、影像学缓解率（85%）和无进展生存期/至进展时间（82%）进行了充分报告，但少数试验纳入了健康相关生活质量。在随机试验（n = 11）中，研究人群更为同质，研究设计更常得到明确界定；然而，只有45%的试验按照实体瘤疗效评价标准规定了基线时的影像学进展，健康相关生活质量的报告率（55%）仍然欠佳。NET临床试验的设计和报告，主要是单臂II期试验，仍然欠佳，尽管我们对NET生物学和独特特征的认识有所增加，但随着时间的推移并没有显著改善。随机试验的质量较高，尽管某些设计和报告要素在一些研究中仍然不足。我们必须优先考虑NET临床试验的设计和实施，以便有效地为未来研究提供信息并指导实践变革。
