Real-world prospective study on compassionate and off-label novel anticancer therapies in children, adolescents, and young adults: The SACHA-INTERNATIONAL ITCC study.

Abstract

e22016 Background: Novel anticancer therapies are regularly prescribed outside their marketing authorization or through compassionate use programs to children, adolescents and young adults. Until recently, safety and efficacy data on those prescriptions were neither prospectively nor systematically collected and pharmacovigilance declarations were largely underreported. Methods: SACHA-INTERNATIONAL (NCT04477681) is a prospective international non-interventional study developed within the Innovative Therapies for Children and adolescents with Cancer (ITCC) Consortium, which documents safety and efficacy data of compassionate and off-label innovative anticancer therapies administered to patients aged ≤ 25 years. SACHA-INTERNATIONAL is built up on the SACHA-France study developed by the French Society of Pediatric Oncology (SFCE) (Berlanga et al. JAMA Netw Open 2023), opened in Q1 2020. SACHA-INTERNATIONAL is adapted to each national regulation with common study objectives and eligibility criteria. Data are collected in a common central database. Since Q3 2023, SACHA-INTERNATIONAL is open in UK, Spain, Denmark and Austria. In Q4 2024, Italy has joined the study. Results: Between 01/01/2020 and 31/12/2024, 1054 compassionate/off-label prescriptions to 942 patients were registered in 59 centers in the 5 participating countries (32 centers in France, 12 in UK, 12 in Spain, 2 in Denmark and 1 in Austria), with a median of 10 patients included per center (range: 1-149). Median age at enrolment was 10.7 years (range 0.1 – 24.9). Eighty-six different drugs were prescribed. Study enrollment has steadily increased: 2020 (n=57), 2021 (n=193), 2022 (n=187), 2023 (n=243), 2024 (n=374). The 2023-2024 period increase is due to the study opening outside France (13 and 131 prescriptions in 2023 and 2024, respectively), but also to the increased off-label prescriptions after clinical trial end of enrollment. Detailed data on diagnostic group and year of inclusion are reported in Table 1. Conclusions: Prospective real-world data collection on compassionate and off-label anticancer therapies is feasible at multicenter and international level. By expanding across multiple countries, the SACHA-INTERNATIONAL study ensures that critical safety and efficacy information is adequately collected and shared with the scientific community. SACHA-INTERNATIONAL study enrolment. Diagnosis group 2020 2021 2022 2023 2024 TOTAL I. Leukemia 4 27 13 31 50 125 II. Lymphomas 3 15 6 6 7 37 III. Central nervous system tumors 28 81 93 90 129 421 IV. Neuroblastoma 1 8 12 53 66 140 V. Retinoblastoma 0 0 0 0 0 0 VI. Renal tumors 1 1 2 1 8 13 VII. Hepatic tumors 2 1 2 3 2 10 VIII. Malignant bone tumors 7 26 21 23 40 117 IX. Soft tissue sarcomas 6 25 17 19 30 97 X. Germ cell and gonadal tumors 0 0 0 1 4 5 XI. Epithelial tumors and melanoma 4 7 10 5 7 33 XII. Other and unspecified 1 2 8 10 22 43