早期免疫肿瘤学试验中的生存率：一种预后指数的开发与验证
Survival in Early Phase Immuno-Oncology Trials: Development and Validation of a Prognostic Index.
作者信息
Day Daphne, Guo Christina, Kanjanapan Yada, Tran Ben, Spreafico Anna, Joshua Anthony M, Wang Lisa, Abdul Razak Albiruni R, Leighl Natasha B, Hansen Aaron R, Butler Marcus O, Siu Lillian L, Desai Jayesh, Bedard Philippe L
机构信息
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
Department of Medicine, University of Toronto, Toronto, Canada.
出版信息
JNCI Cancer Spectr. 2019 Sep 19;3(4):pkz071. doi: 10.1093/jncics/pkz071. eCollection 2019 Dec.
BACKGROUND
Immuno-oncology (IO) is rapidly evolving in early drug development. We aimed to develop and prospectively validate a prognostic index for patients treated in IO phase I trials to assist with patient selection.
METHODS
The development cohort included 192 advanced solid tumor patients treated in 13 IO phase I trials, targeting immune checkpoint and/or co-stimulatory molecules. A prognostic scoring system was developed from multivariate survival analysis of 10 clinical factors, and subsequently validated in two independent validation cohorts (n = 152 and n = 80).
RESULTS
In the development cohort, median age was 57.5 years (range = 20.4-84.8 years). Median progression-free survival and overall survival (OS) were 13.4 and 73.6 weeks, respectively, 90-day mortality was 16%, and overall response rate was 20%. In multivariate analysis, Eastern Cooperative Oncology Group performance status greater than or equal to 1 (hazard ratio [HR] = 3.2, 95% confidence interval [CI] = 1.8 to 5.7; < .001), number of metastatic sites greater than 2 (HR = 2.0, 95% CI = 1.3 to 3.1; = .003), and albumin less than the lower limit of normal (HR = 1.8, 95% CI = 1.2 to 2.7; = .007) were independent prognostic factors; comprising the Princess Margaret Immuno-oncology Prognostic Index (PM-IPI). Patients with a score of 2-3 compared with patients with a score of 0-1 had shorter OS (HR = 3.4, 95% CI = 1.9 to 6.1; < .001), progression-free survival (HR = 2.3, 95% CI = 1.7 to 3.2; < .001), higher 90-day mortality (odds ratio = 8.1, 95% CI = 3.0 to 35.4; < .001), and lower overall response rate (odds ratio = 0.4, 95% CI = 0.2 to 0.8; = .019). The PM-IPI retained prognostic ability in both validation cohorts and performed better than previously published phase I prognostic scores for predicting OS in all three cohorts.
CONCLUSIONS
The PM-IPI is a validated prognostic score for patients treated in phase I IO trials and may aid in improving patient selection.
背景
免疫肿瘤学（IO）在早期药物研发中发展迅速。我们旨在开发并前瞻性验证一种用于IO一期试验中患者的预后指数，以辅助患者选择。
方法
开发队列包括192例接受13项IO一期试验治疗的晚期实体瘤患者，试验靶向免疫检查点和/或共刺激分子。通过对10个临床因素进行多变量生存分析，开发了一种预后评分系统，随后在两个独立的验证队列（n = 152和n = 80）中进行验证。
结果
在开发队列中，中位年龄为57.5岁（范围 = 20.4 - 84.8岁）。中位无进展生存期和总生存期（OS）分别为13.4周和73.6周，90天死亡率为16%，总缓解率为20%。在多变量分析中，东部肿瘤协作组体能状态大于或等于1（风险比[HR] = 3.2，95%置信区间[CI] = 1.8至5.7；P <.001）、转移部位数大于2（HR = 2.0，95% CI = 1.3至3.1；P =.003）以及白蛋白低于正常下限（HR = 1.8，95% CI = 1.2至2.7；P =.007）是独立的预后因素；构成了玛格丽特公主免疫肿瘤预后指数（PM - IPI）。与评分为0 - 1的患者相比，评分为2 - 3的患者OS较短（HR = 3.4，95% CI = 1.9至6.1；P <.001）、无进展生存期较短（HR = 2.3，95% CI = 1.7至3.2；P <.001）、90天死亡率较高（比值比 = 8.1，95% CI = 3.0至35.4；P <.001）且总缓解率较低（比值比 = 0.4，95% CI = 0.2至0.8；P =.019）。PM - IPI在两个验证队列中均保持了预后能力，并且在预测所有三个队列的OS方面比先前发表的一期预后评分表现更好。
结论
PM - IPI是一种经过验证的用于IO一期试验患者的预后评分，可能有助于改善患者选择。
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