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

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). 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. 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). 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. •In Studies 223/213, eribulin alone (223) and in combination with irinotecan (213) was evaluated for pediatric sarcomas.•Pediatric sarcomas included were rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, and Ewing sarcoma.•Twenty-one and 27 patients were treated in Studies 223 and 213, respectively; both studies terminated enrollment early.•No responses were observed in Study 223; three patients in part 2 of Study 213 had a partial response (ORR: 11.1%; CBR: 48.1%).•Eribulin did not demonstrate clinically meaningful activity in these studies; safety profiles were consistent with adults.