Comprehensive nationwide study on the prescription of experimental anticancer therapies for compassionate use in children and adolescents in France

10019 Background: Compassionate use prescriptions of innovative anticancer therapies are common in pediatric oncology, although rarely reported and activity/safety information mainly based on single/limited institutional retrospective experiences. Methods: In France, early drug access before marketing authorization is granted by the French National Agency for the Safety of Medicines and Health Products (ANSM) in case on unmet need, positive benefit/risk balance of preliminary data and no access within clinical trials. All anticancer prescriptions approved by the ANSM from 01/01/2020 to 31/12/2022 for patients < 18 years-old were analyzed. Patients safety and activity data were collected through the SACHA France study (NCT04477681) in the 2020-2021 period. 2022 data analysis is currently ongoing and will be included in the presentation at ASCO. Results: In the study period, 1022 anticancer compassionate use prescriptions were authorized by ANSM. The most frequently prescribed drug was methotrexate drinkable solution (n = 526) and 383 prescriptions were within the inclusion criteria of the SACHA study (anti-cancer innovative therapies not approved in Europe or new formulation of an already approved drug after 2007). In the 2020-2021 period, 28 different therapies were prescribed to 188 patients in a French Society of Pediatric Oncology (SFCE) center. Of them, 14 patients never received the prescribed drug, mainly due to early death. 107 of 174 (61%) eligible patients from 21 SFCE centers were included in the SACHA study (56% in 2020 and 67% in 2021). Median age at inclusion was 6.0 years (range: 0.3 -17.3). Main cancer types were central nervous system (CNS) tumors (69), followed by non-CNS tumors (24) and leukemia/lymphoma (14). Main prescribed therapies targeted MEK/BRAF (66), EZH2 (11), BLC2 (7) and ALK/ROS1/MET (5). In 40/107 patients (37%) at least a grade ≥2 clinical and/or grade ≥3 biological adverse drug reaction (ADR) was reported, leading to delayed therapy in 15 % of patients. Overall, 10 serious ADRs were reported in 10 patients. At last news, 53/107 patients had stopped their drug, mainly due to disease progression (33), followed by physician decision (11) and toxicity ± physician decision (8). 12-months PFS was 49% (95 IC: 38-60 %), with a median of 334 days of follow-up for patients on therapy. Conclusions: To our knowledge, this is the first comprehensive nation-wide study on compassionate use prescriptions of experimental anticancer therapies to children and adolescents with cancer with prospective safety/activity information in more than 60% of patients. This study underscores the importance, and feasibility, of the close collaboration between academia and regulatory authorities to ensure adequate real-life monitoring of these prescriptions. Supported by Imagine for Margo, Association Hubert Gouin, Fondation du LEEM and the SFCE.