Prognostic factors of early mortality in children and adolescents enrolled in oncology trials with a dose-finding part in the era of targeted and immune therapies: An Innovative Therapies for Children with Cancer (ITCC) study

10020 Background: Phase I/II trials play a key role for children with relapsed/refractory tumors. Life expectancy beyond 8-12 weeks is a common eligibility criterion. However, there are no objective means to determine life expectancy for trial candidates. A better understanding of the risk factors associated with early mortality on trial could maximize the efficiency of such trials, whilst ensuring the ethical aspects of recruitment. Methods: Patients with relapsed/refractory solid tumors or lymphomas aged < 18 years and participating in interventional clinical trials with a dose-finding part between 2000-2018 in 14 ITCC centers (across 5 European countries) were eligible. The mortality at 30 and 90 days (30-DM and 90-DM, respectively) from Cycle1-Day1 (C1D1) and its association with clinical, laboratory and efficacy data were assessed. Validated prognostic scores (RMH, MDACC) were correlated with early mortality rates. Results: Overall, 527 cases were included in the study; 19 subjects had participated in > 1 trial, leaving a total of 507 subjects enrolled in their first phase I/II trial. Median age at C1D1 was 11.6 years (range, 0.5-17.9); male:female ratio 1.2:1; central nervous system (CNS) tumors (40%) Vs extra-CNS tumors (60%); 75% cases were treated in trials with at least one targeted therapy. The 30-DM (24/507) and 90-DM (116/507) were 4.7% (95%CI 3.1-7.0) and 23.0% (95%CI 19.3-26.8), respectively. At baseline the clinical variables which correlated with higher 90-DM in the univariate analysis were: performance status (Lansky or Karnofsky) ≤80%, no school/work attendance, requirement of opioids, ≥3 metastatic sites, Hb < 100 g/dL and Total Bilirubin, LDH or AST above normal levels (up to the maximum permitted according to protocol eligibility criteria). Higher RMH and MDACC scores also correlated with higher 90-DM. Conclusions: To our knowledge this is the largest case series of children and adolescents participating in pediatric phase I/II trials to date, in which most of the patients were treated with targeted or immuno-oncology agents. The reported 30-DM and 90-DM will serve as a reference benchmark for future trials. Performance status ≤80%, no school/work attendance, requirement of opioids and ≥3 metastatic sites correlated with higher 90-DM. Adult prognostic scores (RMH, MDACC) showed good correlation with 90-DM in the pediatric population. Prognostic factors of early mortality should be given appropriate relevance at the time of study design, informing families and recruiting patients to these studies.