Mangal Naveen, Salem Ahmed Hamed, Li Mengyao, Menon Rajeev, Freise Kevin J
Center for Pharmacometrics and Systems Pharmacology, University of Florida, Orlando, FL, USA.
Abbvie, Inc., North Chicago, IL, USA.
Hematol Oncol. 2018 Feb;36(1):37-43. doi: 10.1002/hon.2463. Epub 2017 Jul 14.
Demonstration of clinical effectiveness of a non-Hodgkin's lymphoma (NHL) treatment generally involves determination of progression-free survival (PFS). However, the long evaluation time of PFS limits its utility to make timely decisions in drug development. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in NHL. A database was systematically developed from 513 identified NHL trials reported from 1996 to 2015. Potential predictors of the relationship between response rates and PFS were evaluated, including age, sex, treatment, percentage of treatment-naïve patients, and subtype of NHL. Seventy-three trials involving 86 cohorts were included in the meta-analysis. Linear regression analysis using logit of response rates and logarithm of median PFS indicated that the correlation between overall response rate (ORR) and median PFS was higher (R = 0.70) when compared to that of complete response (CR) rate and median PFS (R = 0.57). Furthermore, the correlation was improved with the addition of percentage of treatment-naïve patients and percentage of patients with follicular lymphoma (FL) (P < .005) between ORR and median PFS (R = 0.78), and between CR rate and median PFS relationship (R = 0.74). Treatment was not found to alter this relationship. In summary, ORR is as good as CR rate in predicting median PFS. Moreover, longer median PFS is expected in the trials including treatment-naïve and/or FL patients at a given ORR/CR rate. The determined relationship can be used to project the median PFS based on ORR or CR rate.
非霍奇金淋巴瘤（NHL）治疗临床疗效的证明通常涉及无进展生存期（PFS）的测定。然而，PFS的评估时间较长，限制了其在药物研发中及时做出决策的效用。因此，本分析的目的是确定NHL中缓解率与中位PFS之间的关系。从1996年至2015年报告的513项已识别的NHL试验中系统地建立了一个数据库。评估了缓解率与PFS之间关系的潜在预测因素，包括年龄、性别、治疗、初治患者百分比和NHL亚型。荟萃分析纳入了涉及86个队列的73项试验。使用缓解率的logit和中位PFS的对数进行线性回归分析表明，与完全缓解（CR）率和中位PFS（R = 0.57）相比，总缓解率（ORR）与中位PFS之间的相关性更高（R = 0.70）。此外，在ORR与中位PFS（R = 0.78）以及CR率与中位PFS关系（R = 0.74）之间加入初治患者百分比和滤泡性淋巴瘤（FL）患者百分比后，相关性得到改善（P <.005）。未发现治疗会改变这种关系。总之，在预测中位PFS方面，ORR与CR率一样好。此外，在给定的ORR/CR率下，在包括初治和/或FL患者的试验中预计中位PFS会更长。所确定的关系可用于根据ORR或CR率预测中位PFS。
