Access to innovative therapies outside clinical trials in pediatric oncology: a national real-world analysis of off-label and compassionate use of targeted therapies and immunotherapies
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Targeted therapies and immunotherapies are increasingly used in pediatric oncology; however, many innovative agents are prescribed off-label or through compassionate use programs due to limited pediatric approvals and restricted access to clinical trials. Real-world data on these access pathways remain limited. Methods This retrospective multicenter observational study was promoted by the Italian Association of Pediatric Hematology and Oncology (AIEOP) Working Group on New Drugs. Prescriptions made between 2018 and 2023 for patients aged ≤25 years receiving targeted therapies or immunotherapies through off-label or compassionate use were collected from 19 AIEOP pediatric oncology centers, covering approximately 80% of national pediatric cancer cases. Variables included diagnosis, indication, access modality, regulatory status, molecular rationale, treatment duration, discontinuation. Results A total of 562 prescriptions involving 70 drugs were collected. Off-label prescriptions accounted for 77% (n=431) and compassionate use for 23% (n=131). Treatments were mainly for relapsed (46%) or refractory (35%) disease. The most frequent diagnoses were acute lymphoblastic leukemia (n=119, 21%) and gliomas (n=76, 14%). Molecular alterations supporting treatment selection were reported in a subset, including FLT3 , BCR::ABL1 , BRAF , and MAPK alterations. Median treatment duration was 133 days (interquartile range (IQR), 42–399). Discontinuation was mainly due to disease progression (n=216, 47%), completion of planned therapy (n=175, 38%), or toxicity (n=33, 7%). Lack of clinical trials was the main driver for access (n=438, 78%). Median authorization time was 9.5 days (IQR, 5–15)., with bureaucratic complexity as the main barrier. Conclusions Off-label and compassionate use represented a common access pathway for innovative therapies in Italian pediatric oncology, particularly in relapsed or refractory disease. These findings highlight persistent challenges in pediatric drug development, clinical trial availability, and regulatory pathways.
Source: EJC Paediatric Oncology
Authors: Valeria Ceolin, Luca Bergamaschi, Federico Mercolini, Daniela Di Carlo, Enrico Opocher, Virginia Livellara, Franco Locatelli, Maria Giuseppina Cefalo, Maria Grazia Pionelli, Carmelo Rizzari, Sofia Arnaboldi, Veronica Leoni, Simone Cesaro, Alberto Romano, Antonio Ruggiero, Luisa Di Pasquale, Luca Lo Nigro, Elisa Coassin, Daniela Onofrillo, Camilla Rosa, Francesca Introzzi, Simona Rinieri, Rossella Mura, Letizia Brescia, Loredana Amoroso, Giovanna Sironi, Silvia Sorbara, Nicoletta Bertorello, Michela Casanova, Franca Fagioli
Institutions: Princess Máxima Center, Ospedale Regina Margherita, Fondazione IRCCS Istituto Nazionale dei Tumori, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of Bologna, University of Padua, Istituto Giannina Gaslini, Università Cattolica del Sacro Cuore, Bambino Gesù Children's Hospital, Santobono Children's Hospital, Azienda Ospedaliera Universitaria Integrata Verona, Agostino Gemelli University Polyclinic, Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco", Centro di Riferimento Oncologico, Azienda USL di Pescara, Meyer Children's Hospital, University of Parma, Ospedale di Parma, University of Ferrara, Arcispedale Sant'Anna, Azienda Ospedaliera G. Brotzu, Policlinico Umberto I, Sapienza University of Rome, University of Turin
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,340
OpenAlex ID: W7204699786