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

Abhinav Kurumaddali1, Ahmed Hamed Salem2,3, Suresh K. Agarwal2✉

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

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Citation:
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 http://www.jcancer.org/v10p5427.htm

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Abstract

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