J Cancer 2019; 10(22):5427-5433. doi:10.7150/jca.33175
Short Research Communication
A Meta-Analysis of Higher-risk Myelodysplastic Syndrome Trials to Evaluate the Relationship between Short-term Endpoints and Overall Survival
1. Department of Pharmaceutics, University of Florida, Gainesville, FL
2. Abbvie, Inc., North Chicago, IL
3. Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
Kurumaddali A, Salem AH, Agarwal SK. A Meta-Analysis of Higher-risk Myelodysplastic Syndrome Trials to Evaluate the Relationship between Short-term Endpoints and Overall Survival. J Cancer 2019; 10(22):5427-5433. doi:10.7150/jca.33175. Available from https://www.jcancer.org/v10p5427.htm
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 R2=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.
Keywords: Myelodysplastic syndrome, surrogate endpoints, overall survival, response rates, azacitidine, treatment-naive