A Meta-Analysis of Higher-risk Myelodysplastic Syndrome Trials to Evaluate the Relationship between Short-term Endpoints and Overall Survival.
| Autor: | Kurumaddali A; Department of Pharmaceutics, University of Florida, Gainesville, FL., Salem AH; Abbvie, Inc., North Chicago, IL.; Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt., Agarwal SK; Abbvie, Inc., North Chicago, IL. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of Cancer [J Cancer] 2019 Aug 29; Vol. 10 (22), pp. 5427-5433. Date of Electronic Publication: 2019 Aug 29 (Print Publication: 2019). |
| DOI: | 10.7150/jca.33175 |
| Abstrakt: | Background : The objective of this work was to evaluate the relationship between the response rates and median overall survival (OS) in higher-risk myelodysplastic syndrome (HR-MDS) to determine whether response rates could be used as predictors of median OS. Methods : Relevant MDS clinical trials were identified through a review of published literature. Weighted linear regression was performed with various linearizing transformations of response rates and median OS using the in-house built HR-MDS clinical trials database. 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-five trials involving 38 cohorts were included in the meta-analysis. The analysis demonstrated that partial response (PR) or better rate (sum of complete response (CR), marrow complete response (mCR) and PR rates) was a strong predictor of median OS (adjusted R 2 =0.64). The median OS was 3.3 months longer (P < 0.005) with azacitidine treatment compared to treatment with other drugs for a given response rate and prior therapy status. We also have shown that the median OS of treatment naïve HR-MDS patients was 4.5 months longer (P < 0.0001) compared to that of previously treated patients for a given response rate and treatment group. Conclusion : Significant correlation between PR or better rate and median OS in HR-MDS highlights the potential to use PR or better rate as a surrogate endpoint to accelerate development of novel therapies for MDS. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).) |
| Databáze: | MEDLINE |
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