A meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma

Kazuhiro Tanaka,Hiroshi Tsumura,Masanori Kawano,Ichiro Itonaga,Tatsuya Iwasaki

doi:10.1186/s12885-020-06871-9

Kazuhiro Tanaka, Hiroshi Tsumura + Show 3 more

Open Access

https://doi.org/10.1186/s12885-020-06871-9

Copy DOI

Journal: BMC Cancer	Publication Date: May 5, 2020
Citations: 3	License type: open-access

Affiliation: Oita University

Abstract

BackgroundIn randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the correlation between EFS and OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach.MethodsWe identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated using weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2).ResultsA total of 3612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis revealed that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929).ConclusionsOverall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. EFS may be a useful endpoint in RCTs of ES chemotherapy, and it is worth verifying using individual patient data.

Highlights

In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS)
Study selection and data extraction Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [3], we conducted a systematic search of PubMed, Scopus, EBSCOhost MEDLINE, and the Cochrane Central Register of Controlled Trials
The remaining 7 RCTs were considered eligible for the meta-analysis (Fig. 1)

Summary

Introduction

In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). Ewing sarcoma (ES) is the second most frequent malignant bone tumor in children. It accounts for only 1% of all childhood cancers in the United States [1]. Event-free survival (EFS) has, been used as the primary endpoint in many RCTs of ES. EFS is an important measure that indicates the disease-free period in an adjuvant setting trial; it is a meaningful outcome in its own right, especially in RCTs of pediatric cancer treatment. The correlation between EFS and OS in RCTs of ES therapy has not yet been investigated

Objectives

Methods

Results

Discussion

Conclusion