Efficacy, safety, and pharmacokinetics of eribulin as monotherapy or in combination with irinotecan for patients with pediatric rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, or Ewing sarcoma

Background: In this report, we present results from studies of eribulin as monotherapy (Study 223) and in combination with irinotecan (the phase II part of Study 213) for patients with relapsed/refractory pediatric rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), or Ewing sarcoma (EWS). Patients and methods: Studies 223 and 213 were phase II multicenter trials that enrolled pediatric patients with histologically confirmed disease. Treatment comprised 21-day cycles of eribulin mesylate 1.4 mg/m² on days 1 and 8 (Study 223) or eribulin 1.4 mg/m² on days 1 and 8 plus irinotecan 40 mg/m² on days 1-5 (Study 213). For both studies, the primary endpoints were objective response rate (ORR) and duration of response (DOR); secondary endpoint included safety. Results: In Study 223, 21 patients (RMS, n = 8; NRSTS, n = 8; EWS, n = 5) were enrolled and treated. No responses were observed, resulting in early termination of enrollment. By the data cut-off date (22 February 2021), six patients (RMS, n = 3; NRSTS, n = 1; EWS, n = 2) had stable disease for ≥5 weeks. All patients had one or more treatment-emergent adverse event (TEAE), most commonly neutrophil count decreased (71.4%). In Study 213 (phase II part), 27 patients (RMS, n = 9; NRSTS, n = 9; EWS, n = 9) were enrolled/treated. By the data cut-off date (9 July 2021), three patients (one in each cohort) had had a response, resulting in an ORR of 11.1% and DORs of 2.9 (RMS), 1.4 (NRSTS), and 15.4 (EWS) months. All patients had one or more TEAE, most commonly diarrhea and neutrophil count decreased (51.9% each). Conclusions: Eribulin, as monotherapy or combination therapy, exhibited a safety profile consistent with that observed previously in adult populations; however, efficacy in both studies was not considered adequate to advance investigation in these disease areas.