TY - JOUR
T1 - 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
AU - Casanova, M.
AU - Albert, C. M.
AU - Bautista, F.
AU - Borinstein, S. C.
AU - Bradfield, S.
AU - Bukowinski, A.
AU - Campbell-Hewson, Q.
AU - Hawkins, D. S.
AU - Kim, A.
AU - Milano, G. M.
AU - Marshall, L. V.
AU - Pinto, N.
AU - Pratilas, C. A.
AU - Rubio-San-Simón, A.
AU - Windsor, R.
AU - Majid, O.
AU - Scott, R.
AU - Jia, Y.
AU - Paoletti, C.
AU - Kontny, U.
N1 - Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2025/2
Y1 - 2025/2
N2 - 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.
AB - 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.
KW - Ewing sarcoma
KW - eribulin
KW - pediatric
KW - pharmacokinetics
KW - soft tissue sarcoma
KW - Humans
KW - Rhabdomyosarcoma/drug therapy
KW - Child, Preschool
KW - Sarcoma/drug therapy
KW - Male
KW - Treatment Outcome
KW - Furans/administration & dosage
KW - Polyether Polyketides
KW - Ketones/administration & dosage
KW - Adolescent
KW - Female
KW - Sarcoma, Ewing/drug therapy
KW - Irinotecan/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Child
KW - Camptothecin/analogs & derivatives
UR - https://www.scopus.com/pages/publications/85216724195
UR - https://www.mendeley.com/catalogue/b986cff7-4779-3174-a867-89bb5fafc5a1/
U2 - 10.1016/j.esmoop.2024.104129
DO - 10.1016/j.esmoop.2024.104129
M3 - Article
C2 - 39908698
AN - SCOPUS:85216724195
SN - 2059-7029
VL - 10
JO - ESMO Open
JF - ESMO Open
IS - 2
M1 - 104129
ER -