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

ABSTRACT

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.