(P 13) OUTCOME OF PATIENTS WITH RELAPSED OR REFRACTORY NON-RHABDOMYOSARCOMA SOFT TISSUE SARCOMAS ENROLLED IN PHASE II COOPERATIVE GROUP CLINICAL TRIALS: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP

Objective: Nearly 25% to 30% of children and young adults with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) suffer a relapse or progression following first-line treatment. No clinical trials have solely focused on treating children and young adults with relapsed or refractory NRSTS; thus, data on outcomes for this population are lacking. The primary objective of our analysis was to estimate the event-free survival (EFS) of children and young adults with relapsed or refractory NRSTS treated in single-arm phase II studies conducted by the Children’s Oncology Group (COG) and predecessor groups to establish a benchmark EFS as a primary endpoint for future phase II NRSTS trials. The secondary objectives were to compare the EFS by the pre-defined patient- disease- and trial-related characteristics and type of radiographic response and estimate the overall survival (OS).

Methods: A retrospective analysis of recurrent or refractory NRSTS patients enrolled in single-arm phase II COG, Pediatric Oncology Group and Children’s Cancer Group trials between 1999 and 2015 was conducted. We used the Kaplan-Meier Method to estimate EFS and OS. The EFS was defined as disease progression/relapse or death. The Log-rank test was used to compare the EFS distribution between prespecified subgroups based on age at enrollment, sex, race/ethnicity, NRSTS histology, prior lines of therapy, calendar year of trial and type of radiographic response. A two-sided p-value < 0.05 was considered statistically significant.

Results: Our analysis included 137 patients [median age: 17 years (range: 1.6-26.9)] enrolled in thirteen phase II trials. All trials used response rate as the primary endpoint incorporating either WHO or RECIST radiographic response criteria. Of the 121 patients with evaluable radiographic response, 96 (70.1%) had progressive disease (PD), 22 (16.1%) had stable disease (SD), 3 (2.2%) achieved complete response (CR) while no patient had a partial response. None of the agents used in the trials were considered active based on the trial-specified response rates. The median duration of follow-up for the patients that were event-free at the last follow-up was three years. The estimated 6-month EFS of the entire study cohort was 19.4% [95% Confidence Interval (CI): 12.7%-26%)] (Figure 1). No significant difference in 6-months EFS was observed by age at enrollment [<=15 years vs. > 15 years (24.1% vs. 18.2%)], race/ethnicity [Black or African American vs. other vs. White (47.6% vs. 22.2% vs. 15.3%)], sex [female vs. male (17.6% vs. 20.4%)], histology subtype [synovial sarcoma (22%, 95% CI: 9.3% to 34.6%), desmoplastic small round cell tumor (18%, 95% CI: 0% to 37.9%) and malignant peripheral nerve sheath tumors (19.1%, 95% CI 7.9% to 30.4%)], by prior lines of therapies [1 or 2 lines vs. 1 or more lines (18.9% vs. 19.5%)] and by trial initiation year [before year 2006 vs. after year 2006 (23.2% vs.15.2%)]. The 6-month EFS significantly differed by the type of radiographic response (PD vs. SD vs. CR: 11.5% vs. 47.8% vs. 33.3%, P= < 0.0001). The 1-year and 2-year OS of the whole study cohort was 33.8% (95% CI: 25.5% to 42%) and 16.1% (95% CI: 8.9% to 23.4%), respectively (Figure 2).

Conclusion: The EFS and OS for children and young adults with relapsed or refractory NRSTS remain suboptimal. We have established baseline EFS outcomes that can be referenced as a benchmark for future single-arm phase II trials incorporating potentially active novel agents in this population.