Targeted Therapy and Oral Chemotherapy as Maintenance Treatment in Pediatric Very‐High‐Risk and High‐Risk Rhabdomyosarcoma: A Retrospective Study of Efficacy and Safety

Maintenance therapy (MT) and targeted drugs have improved the survival of patients with high-risk rhabdomyosarcoma (RMS) in clinical trials. However, there are limited data concerning targeted drugs and oral chemotherapy for MT in pediatric patients with very-high-risk (VHR) and high-risk (HR) RMS. Here, we evaluated the safety and effectiveness of these regimens and aimed to identify circulating tumor DNA (ct-DNA) markers associated with prognosis. We retrospectively retrieved data for 102 pediatric patients with VHR or HR RMS who underwent MT at Sun Yat-sen University Cancer Center from January 2011 to March 2025 involving targeted drugs plus oral chemotherapy (subgroup 1); targeted drugs (subgroup 2); and oral chemotherapy (subgroup 3). Ct-DNA markers were examined throughout treatment and at follow-up. Subgroups 1 and 2 comprised 14 and seven VHR RMS patients, respectively, and subgroup 3 consisted of 39 VHR and 42 HR RMS patients. With a median follow-up of 32 months, no significant differences among subgroups in duration of remission (p = 0.56) or 2-year event-free survival (p = 0.78) were observed. PAX-FOXO1 fusion (p = 0.01), CDK4 mutation (p = 0.02), and TP53 mutation (p = 0.02) were independently associated with unfavorable duration of remission. No grade 3 or higher treatment-related adverse events were observed. MT with targeted drugs shows comparable efficacy in VHR and HR pediatric RMS patients, with manageable adverse reactions. Longitudinal ct-DNA testing could guide treatment decision-making and prognostic stratification for these patients.