Measuring Safety and Outcomes for the Use of Compassionate and Off-Label Therapies for Children, Adolescents, and Young Adults With Cancer in the SACHA-France Study
Authors: Berlanga Pablo , Ndounga-Diakou Lee Aymar , Aerts Isabelle , Corradini Nadège , Ducassou Stéphane , Strullu Marion , de Carli Emilie , André Nicolas , Entz-Werle Natacha , Raimbault Sandra , Roumy Marianne , Renouard Marjolaine , Gueguen Gwenaelle , Plantaz Dominique , Reguerre Yves , Cleirec Morgane , Petit Arnaud , Puiseux Chloe , Andry Leslie , Klein Sébastien , Bodet Damien , Kanold Justyna , Briandet Claire , Halfon-Domenech Carine , Nelken Brigitte , Piguet Christophe , Saumet Laure , Chastagner Pascal , Benadiba Joy , Millot Frédéric , Pluchart Claire , Schneider Pascale , Thouvenin Sandrine , Gambart Marion , Serre Jill , Abbou Samuel , Leruste Amaury , Cayzac Hélena , Gandemer Virginie , Laghouati Salim , Vassal Gilles 
Published: July 2023

ImportanceInnovative anticancer therapies for children, adolescents, and young adults are regularly prescribed outside their marketing authorization or through compassionate use programs. However, no clinical data of these prescriptions is systematically collected.ObjectivesTo measure the feasibility of the collection of clinical safety and efficacy data of compassionate and off-label innovative anticancer therapies, with adequate pharmacovigilance declaration to inform further use and development of these medicines.Design, Setting, and ParticipantsThis cohort study included patients treated at French pediatric oncology centers from March 2020 to June 2022. Eligible patients were aged 25 years or younger with pediatric malignant neoplasms (solid tumors, brain tumors, or hematological malignant neoplasms) or related conditions who received compassionate use or off-label innovative anticancer therapies. Follow up was conducted through August 10, 2022.ExposuresAll patients treated in a French Society of Pediatric Oncology (SFCE) center.Main Outcomes and MeasuresCollection of adverse drug reactions and anticancer activity attributable to the treatment.ResultsA total of 366 patients were included, with a median age of 11.1 years (range, 0.2-24.6 years); 203 of 351 patients (58%) in the final analysis were male. Fifty-five different drugs were prescribed, half of patients (179 of 351 [51%]) were prescribed these drugs within a compassionate use program, mainly as single agents (74%) and based on a molecular alteration (65%). Main therapies were MEK/BRAF inhibitors followed by multi-targeted tyrosine kinase inhibitors. In 34% of patients at least a grade 2 clinical and/or grade 3 laboratory adverse drug reaction was reported, leading to delayed therapy and permanent discontinuation of the innovative therapy in 13% and 5% of patients, respectively. Objective responses were reported in 57 of 230 patients (25%) with solid tumors, brain tumors, and lymphomas. Early identification of exceptional responses supported the development of specific clinical trials for this population.Conclusions and RelevanceThis cohort study of the SACHA-France (Secured Access to Innovative Medicines for Children with Cancer) suggested the feasibility of prospective multicenter clinical safety and activity data collection for compassionate and off-label new anticancer medicines. This study allowed adequate pharmacovigilance reporting and early identification of exceptional responses allowing further pediatric drug development within clinical trials; based on this experience, this study will be enlarged to the international level.