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

Abstract

Background: 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). 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. Methods: We 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 (R 2). Results: A 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 (R 2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R 2 = 0.818, ρ = 0.929). Conclusions: Overall, 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.

Surrogacy analysis of intermediate end-points for overall survival in randomized controlled trials of rhabdomyosarcoma

“…In contrast, the correlation between 1-, 3-, and 5-year OS and OS HR improved accordingly. This result is similar to that previously reported for osteosarcoma 12 and Ewing sarcoma 24 . Table 4.…”

An Immune Cell Signature Is Associated With Disease-Free Survival and Adjuvant Chemosensitivity of Patients With Resectable Gastric Cancer

“…Moreover, other than previous studies which generated models mostly based on OS ( 11 , 31 , 32 ), our study mainly focused on the DFS of GC patients. Though OS is a recognized and widely used outcome measure for patients with tumors, its use as a marker of therapeutic benefit remains controversial ( 33 , 34 ). Recurrence and metastasis are the two important factors shortening the OS of patients, indicating that it is essential to assess the relapse risk accurately to improve prognosis.…”

Recent and Ongoing Research into Metastatic Osteosarcoma Treatments

“…In practice, however, progression-free survival (PFS) (or “event-free survival”; EFS) is more commonly used as a primary endpoint in phase II trials. Concerningly, while PFS and OS data correlated tightly in trials involving Ewing sarcoma patients [ 178 ], PFS was a less accurate predictor of OS in trials of localized osteosarcoma patients [ 179 ]. As mentioned above, delayed progression may not foretell prolonged survival, “progression” is more subjective than death, so bias must be avoided, and inconsistencies in the timing of progression monitoring between groups may lead to spurious apparent differences in outcomes [ 180 , 181 ].…”