Response Rates as Predictors of Overall Survival: A Meta-Analysis of Acute Myeloid Leukemia Trials.

Autor:	Agarwal SK; Abbvie, Inc., North Chicago, IL, USA., Mangal N; Abbvie, Inc., North Chicago, IL, USA.; Center for Pharmacometrics and Systems Pharmacology, University of Florida, Orlando, FL, USA., Menon RM; Abbvie, Inc., North Chicago, IL, USA., Freise KJ; Abbvie, Inc., North Chicago, IL, USA., Salem AH; Abbvie, Inc., North Chicago, IL, USA.; Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Jazyk:	angličtina
Zdroj:	Journal of Cancer [J Cancer] 2017 Jun 03; Vol. 8 (9), pp. 1562-1567. Date of Electronic Publication: 2017 Jun 03 (Print Publication: 2017).
DOI:	10.7150/jca.18686
Abstrakt:	Background: Response rates such as overall response rate (ORR), complete response (CR) and complete response with incomplete blood recovery (CRi) can be evaluated in a much shorter period of time than overall survival (OS), potentially accelerating decision making during drug development. The objective of this work was to evaluate the relationship between ORR, CR, CRi or better (CRi+CR) rates and median OS to determine whether response rates could be used as predictors of median OS in acute myeloid leukemia (AML). Methods: A review of published literature was conducted to identify relevant AML clinical trials. Weighted linear regression was performed with various linearizing transformations of response rates and median OS. Covariates of interest were evaluated using a forward inclusion, backward elimination covariate model building procedure at α=0.01 and α=0.005, respectively. Results: Twenty trials involving 26 cohorts were included in the meta-analysis. Azactidine treatment was a significant predictor with longer OS compared to decitabine or low dose cytarabine for a given response rate (P < 0.005). Linear regression analysis indicated that the correlation of both CRi or better rates and CR rates with median OS was higher than that of ORR with median OS. The final model showed a strong correlation between CRi or better rates and median OS (R 2 =0.66). Conclusion: Significant correlation between CRi or better rates and median OS in AML highlights the potential for CRi or better rate, in addition to CR rate, to serve as surrogate markers for median OS. Competing Interests: Competing Interests: AbbVie participated in database preparation, data analysis, writing, reviewing and approval of the manuscript. SKA, RM, KJF, and AHS are AbbVie employees and may hold AbbVie stock and/or stock options. NM is a former intern of AbbVie.
Databáze:	MEDLINE
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