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Multicenter Study
. 2023 Jul 3;6(7):e2321568.
doi: 10.1001/jamanetworkopen.2023.21568.

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

Pablo Berlanga  1 , Lee Aymar Ndounga-Diakou  2 , Isabelle Aerts  3 , Nadège Corradini  4 , Stéphane Ducassou  5 , Marion Strullu  6 , Emilie de Carli  7 , Nicolas André  8 , Natacha Entz-Werle  9 , Sandra Raimbault  10 , Marianne Roumy  7 , Marjolaine Renouard  3 , Gwenaelle Gueguen  1 , Dominique Plantaz  11 , Yves Reguerre  12 , Morgane Cleirec  13 , Arnaud Petit  14 , Chloe Puiseux  15 , Leslie Andry  16 , Sébastien Klein  17 , Damien Bodet  18 , Justyna Kanold  19 , Claire Briandet  20 , Carine Halfon-Domenech  21 , Brigitte Nelken  22 , Christophe Piguet  23 , Laure Saumet  24 , Pascal Chastagner  25 , Joy Benadiba  26 , Frédéric Millot  27 , Claire Pluchart  28 , Pascale Schneider  29 , Sandrine Thouvenin  30 , Marion Gambart  31 , Jill Serre  32 , Samuel Abbou  1 , Amaury Leruste  3 , Hélena Cayzac  2 , Virginie Gandemer  15 , Salim Laghouati  2 , Gilles Vassal  1
Affiliations
Multicenter Study

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

Pablo Berlanga et al. JAMA Netw Open. .

Abstract

Importance: Innovative 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.

Objectives: To 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 participants: This 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.

Exposures: All patients treated in a French Society of Pediatric Oncology (SFCE) center.

Main outcomes and measures: Collection of adverse drug reactions and anticancer activity attributable to the treatment.

Results: A 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 relevance: This 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Berlanga reported serving as an advisor without compensation for EUSA Pharma and grants and drugs for trials from Bayer outside the submitted work. Dr André reported travel funding from Roche, drugs used in trials provided by Bristol Myers Squibb, Merck, and Pierre Fabre, and personal fees from Accord HealthCare IDMC outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Drugs Included in the SACHA-France Study
See this image and copyright information in PMC

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