Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Long-term outcomes from Children's Oncology Group study AEWS0031 were assessed to determine whether the survival advantage of interval-compressed chemotherapy (ICC) was maintained over 10 years in patients with localized Ewing sarcoma (ES). AEWS0031 enrolled 568 eligible patients. Patients were randomly assigned to receive vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide alternating once every 3 weeks (standard timing chemotherapy [STC]) versus once every 2 weeks (ICC). For this updated report, one patient was excluded because of uncertainty of original diagnosis. The 10-year event-free survival (EFS) was 70% with ICC compared with 61% with STC (P = .03), and 10-year overall survival (OS) was 76% with ICC compared with 69% with STC (P = .04). There was no difference in the 10-year cumulative incidence of second malignant neoplasms (SMNs; P_C [see Data Supplement, online only] = .5). A test for interaction demonstrated that ICC provided greater risk reduction for patients with tumor volume ≥200 mL than for patients with tumors <200 mL, but no evidence for a significant interaction in other subgroups defined by age, primary site, and histologic response. With longer-term follow-up, ICC for localized ES is associated with superior EFS and OS without an increased risk for SMN compared with STC. ICC is associated with improved outcomes even in adverse-risk patient groups.

Trial registration: ClinicalTrials.gov NCT00006734.

FIG 1.

Comparison of survival by assigned treatment regimen: (A) EFS and (B) OS. EFS, event-free survival; OS, overall survival.

FIG A1.

Comparison of EFS by assigned treatment regimen for patients (A) age <18 years and (B) age ≥18 years, and with (C) nonpelvic primary site and (D) pelvic primary site. EFS, event-free survival.

FIG A2.

Comparison of EFS by assigned treatment regimen for patients with tumor volume (A) <200 mL and (B) ≥200 mL. Comparison of EFS from time of surgical local control by assigned treatment regimen for patients with (C) NVT and (D) AVT. AVT, any viable tumor; EFS, event-free survival; NVT, no viable tumor.

FIG A3.

EFS from time of surgical local control for different histologic response categories (regimens combined). EFS, event-free survival.