Table_3_Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram.docx

IntroductionIdentifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations.Patients and methodsWe retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation.ResultsA total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36–0.91, p 0.02) and number of metastatic sites (

引言：在药物研发领域，识别哪些患者可能从免疫治疗早期临床试验中获益是一项未满足的需求。在众多提出的预后评分中，尚未有评分在接受免疫调节剂（IMAs）联合治疗的病患中得到验证。研究方法：本研究回顾性收集了我院208名接受免疫调节剂早期临床试验的患者数据，将临床和血液相关变量与总生存期（OS）进行相关性分析。同时，使用帝国理工学院（伦敦汉默史密斯医院，英国）接受免疫调节剂治疗的50名患者的回顾性队列进行验证。研究结果：共选取173名受试者进行分析。最常见癌症包括非小细胞肺癌（26%）、肝细胞癌（21.5%）和胶质母细胞瘤（13%）。多因素分析（MVA）显示，与总生存期独立相关的三个因素为：治疗线（二线和三线与后续线相比，HR 0.61，95% CI 0.40-0.93，p 0.02）、连续变量血清白蛋白（HR 0.57，95% CI 0.36–0.91，p 0.02）和转移灶数量（HR 0.83，95% CI 0.67-1.03，p 0.07）。