(P 148) ANALYSIS OF REECUR TRIAL DATA TO EVALUATE POTENTIAL PROGNOSTIC FACTORS IN RECURRENT AND PRIMARY REFRACTORY EWING SARCOMA (RR-ES)

Objective: rEECur is the first randomized controlled trial comparing five chemotherapy regimens commonly used for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES). Patient characteristics, details of previous treatment and measures of disease severity were collected at baseline. Selected prognostic factors from observational studies in RR-ES were used to stratify patients in rEECur but have not been formally analysed within a large randomized trial. The wealth of trial data provides a unique opportunity to explore possible prognostic factors in this patient cohort to inform future translational research and clinical trials.

Methods: Patients aged 4-50 with RR-ES were randomised using a minimisation algorithm to one of five chemotherapy regimens: topotecan/cyclophosphamide, irinotecan/temozolomide, gemcitabine/docetaxel, high dose ifosfamide and carboplatin/etoposide. The stratification factors were: disease type (primary refractory; 1st recurrence < 2 years; 1st recurrence ≥ 2 years; 2nd or subsequent recurrences), site(s) of progressive disease (local progression of primary tumour; pleuropulmonary metastases only; other or combined metastatic progression) and whether RECIST v1.1 measurable or non-measurable disease was present. Additional patient characteristics were collected at baseline including age, sex, pubertal status, renal function, previous cumulative alkylator dose, previous myeloablative therapy and pathognomonic gene fusion details. The primary outcome for the trial was event-free survival (EFS) and will be used to evaluate prognostic effects for each variable of interest as a hazard ratio (HR) and 95% confidence intervals (CI). Each stratification factor will be modelled with EFS and overall survival (OS), adjusting for treatment allocation, to confirm prognostic value in RR-ES. Models will adjust for treatment allocation and the stratification factors. Continuous variables such as age will not be dichotomised for this analysis.

Results: Selected preliminary results are shown. More complete results with updated follow up will be presented at the meeting. In total 487 patients were recruited to the trial between 18DEC2014 and 29APR2022. Median follow-up for these patients is 46 months (95% CI: 36 months, 53 months). The stratification variables and additional baseline variables have been described in Table 1.

Median EFS in this patient population is 4.6 months (95% CI: 3.5 months, 5.3 months). Table 2 details preliminary analysis of the prognostic effect of each stratification variable adjusting for patients’ treatment allocation and the other baseline variables adjusting for treatment allocation and the stratification variables, with EFS. Results based on additional follow up data will be presented at the meeting.

Conclusion: There is evidence that the timing of first progression is prognostic of EFS when adjusting for treatment allocation within this patient cohort; patients with primary refractory disease have a significantly increased risk of progression or death than patients whose disease progresses after treatment but within two years of diagnosis, who have increased risk of progression or death compared to those who progress beyond two years from diagnosis.
These have been proposed in previous observational studies and confirmed within the prospective rEECur patient cohort. Additional patient characteristics will be presented that are novel potentially prognostic factors of EFS and OS in RR-ES.

Table 1_.docx

Table 2_.docx