Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials
Year: 2025
Type: article
Abstract: PURPOSE Outcome of patients with localized osteosarcoma is challenging. The role of mifamurtide is still a matter of debate. Two prospective trials were carried out in Italy (ISG/OS-2) and Spain (GEIS-33) with mifamurtide in ABCB1/P-glycoprotein (Pgp)–positive patients. PATIENTS AND METHODS Patients age ≤40 years with localized extremity high-grade osteosarcoma were eligible. Analysis of Pgp expression from diagnostic biopsy was centralized. Patients received two cycles of preoperative methotrexate, doxorubicin, and cisplatinum (MAP) before surgery. Postoperatively, in case of Pgp overexpression (Pgp-positive), mifamurtide was added, combined with doxorubicin (one cycle) and four consecutive cycles of high-dose ifosfamide (HDIFO) for patients with poor histologic response, or with MAP in case of good response. Patients who were Pgp-negative received MAP postoperatively. We present the merged analysis of ISG/OS-2 and GEIS-33 trial, an observational study with same inclusion criteria and treatment of ISG/OS-2. The primary endpoint was 5-year event-free survival (EFS) according to the use of mifamurtide. Secondary endpoint was overall survival (OS). RESULTS From March 2013 to April 2018, 398 patients were analyzed. The median age was 14 years (range, 4-40), male/female: 238/160 (1.48/1.0); 211 of 398 (53%) tumors were Pgp-positive, and 204 of 398 (51.3%) patients received mifamurtide. With a median follow-up of 70 months (IQR, 49-90 months), the 5-year EFS and OS were 65.2% (95% CI, 60.1 to 69.8) and 74.8% (95% CI, 69.8 to 79.0), respectively, with superior EFS for patients undergoing mifamurtide and chemotherapy as compared with EFS of patients undergoing chemotherapy alone (5-year EFS 71.4% v 58.3%; P = .0139) not confirmed at multivariable analysis ( P = .0593). CONCLUSION In this merged analysis with a risk-adapted strategy for nonmetastatic osteosarcoma, the group with unfavorable prognoses, identified by Pgp expression, performed well when mifamurtide, combined with HDIFO in case of poor response, was administered after surgery.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-25-00210
Authors: Emanuela Palmerini, Cristina Meazza, Angela Tamburini, Catalina Márquez-Vega, Gianni Bisogno, Franca Fagioli, Virginia Ferraresi, Giuseppe Maria Milano, Luca Coccoli, Alba Rubio-San-Simón, Oscar Gallego, María Esther Llinares Riestra, Carla Manzitti, Jaume Mora, Mᵃ Ángeles Vaz-Salgado, Roberto Luksch, Cristina Mata, Michela Pierini, Elisa Carretta, Marilena Cesari, Anna Paioli, Andrea Marrari, Katia Scotlandi, Massimo Serra, Sebastian Dorin Asaftei, Marco Gambarotti, Piero Picci, Stefano Ferrari, Claudia Valverde, Toni Ibrahim, Javier Martín Broto
Institutions: University of Miami, Istituto Ortopedico Rizzoli, Sylvester Comprehensive Cancer Center, Fondazione IRCCS Istituto Nazionale dei Tumori, Meyer Children's Hospital, Hospital Universitario Virgen del Rocío, University of Padua, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Ospedale Regina Margherita, Instituto Nazionale Tumori Regina Elena, Bambino Gesù Children's Hospital, Istituti di Ricovero e Cura a Carattere Scientifico, Hospital Infantil Universitario Niño Jesús, Hospital de Sant Pau, Hospital Universitario Virgen de la Arrixaca, Istituto Giannina Gaslini, Hospital Sant Joan de Déu Barcelona, Hospital Universitario Ramón y Cajal, Hospital General Universitario Gregorio Marañón, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario General de Villalba
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Genentech
OpenAlex ID: W4413273654