Outcome of patients with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcomas enrolled in phase 2 cooperative group clinical trials: A report from the Children’s Oncology Group

Abstract Background The aim of this study was to estimate the event‐free survival (EFS) of children and young adults with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) treated in nonrandomized phase 2 studies conducted by the Children’s Oncology Group (COG) and predecessor groups to establish a benchmark EFS for future phase 2 NRSTS trials evaluating the activity of novel agents. Methods A retrospective analysis of patients with recurrent or refractory NRSTS prospectively enrolled in nonrandomized phase 2 COG and predecessor group trials between 1994 and 2015 was conducted. EFS was defined as disease progression/relapse or death and calculated via the Kaplan–Meier method. The log‐rank test and relative risk regression were used to compare EFS distribution by age at enrollment, sex, race, NRSTS histology, prior lines of therapy, calendar year of trial, and type of radiographic response. Results In total, 137 patients were enrolled in 13 phase 2 trials. All trials used radiographic response rate as a primary outcome, and none of the agents used were considered active on the basis of trial‐specified thresholds. The estimated median EFS and 6‐month EFS of the entire study cohort was 1.5 months (95% confidence interval CI, 1.3–1.8 months) and 19.4% (95% CI, 12.7%–26%), respectively. No difference in EFS was observed by age at enrollment, sex, race, NRSTS histology subtype, prior lines of therapies, and trial initiation year. EFS significantly differed by radiographic response. Conclusions The EFS for children and young adults with relapsed or refractory NRSTS remains suboptimal. Established EFS can be referenced as a benchmark for future single‐agent phase 2 trials incorporating potentially active novel agents in this population.