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

Author:

Berlanga Pablo1,Ndounga-Diakou Lee Aymar2,Aerts Isabelle3,Corradini Nadège4,Ducassou Stéphane5,Strullu Marion6,de Carli Emilie7,André Nicolas8,Entz-Werle Natacha9,Raimbault Sandra10,Roumy Marianne7,Renouard Marjolaine3,Gueguen Gwenaelle1,Plantaz Dominique11,Reguerre Yves12,Cleirec Morgane13,Petit Arnaud14,Puiseux Chloe15,Andry Leslie16,Klein Sébastien17,Bodet Damien18,Kanold Justyna19,Briandet Claire20,Halfon-Domenech Carine21,Nelken Brigitte22,Piguet Christophe23,Saumet Laure24,Chastagner Pascal25,Benadiba Joy26,Millot Frédéric27,Pluchart Claire28,Schneider Pascale29,Thouvenin Sandrine30,Gambart Marion31,Serre Jill32,Abbou Samuel1,Leruste Amaury3,Cayzac Hélena2,Gandemer Virginie15,Laghouati Salim2,Vassal Gilles1

Affiliation:

1. Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France

2. Pharmacovigilance Unit, Clinical Research Direction, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France

3. SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), Institut Curie, PSL Research University, Paris, France

4. Paediatric Haematology-Oncology Institut, of Centre Léon Bérard, Lyon, France

5. Paediatric Haematology-Oncology Department, Centre Hospitalier Universitaire (CHU), Bordeaux, France

6. Paediatric Immuno-Haematology Department, Hôpital Robert-Debré AP-HP, Paris, France

7. Department of Pediatric Oncology, University Hospital, Angers, France

8. Department of Pediatric Hematology & Oncology, Hôpital de La Timone, AP-HM, Marseille, France

9. Pediatric Onco-Hematology Unit, University Hospital of Strasbourg, Strasbourg, France

10. Department of Pediatric Oncology, Oscar Lambret Cancer Center, Lille, France

11. Department of Pediatric Onco-Immuno-Hematology, Grenoble Alpes University Hospital, Grenoble, France

12. Pediatric Oncology and Hematology Unit, CHU Saint Denis de la Réunion, Bellepierre, France

13. Pediatric Immuno-Hemato-Oncology Unit, CHU Nantes, Nantes, France

14. Department of Pediatric Hematology and Oncology, Hôpital Armand Trousseau, Paris, France

15. Department of Pediatric Hemato-Oncology, University Hospital of Rennes, Rennes, France

16. Department of Pediatric Oncology, CHU Amiens Picardie, Amiens, France

17. Pediatric Oncology and Hematology, CHU Jean-Minjoz, Besançon, France

18. Department of Pediatric Hematology and Oncology, University Hospital of Caen, Caen, France

19. Department of Pediatric Hematology-Oncology, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France

20. Pediatric Oncology, CHU Dijon-Bourgogne, Dijon, France

21. Department of Pediatric Hematology-Oncology, University Hospital of Lyon, Lyon, France

22. Department of Pediatric Hematology-Oncology, Jeanne de Flandre Hospital, CHRU, Lille, France

23. Pediatric Oncology, CHU Limoges, Limoges, France

24. Department of Pediatric Hematology-Oncology, University Hospital of Montpellier, Montpellier, France

25. Department of Pediatric Hematology-Oncology, Children’s Hospital of Brabois, Vandoeuvre Les Nancy, France

26. Department of Hemato-Oncology Pediatric, Nice University Hospital, Nice, France

27. Department of Paediatric Haematology and Oncology, Centre Hospitalo-Universitaire de Poitiers, Poitiers, France

28. Department of Paediatric Haematology and Oncology, Centre Hospitalo-Universitaire de Reims, Reims, France

29. Department of Pediatric Hematology and Oncology, Centre Hospitalo-Universitaire de Rouen, Rouen, France

30. Department of Pediatric Hematology-Oncology, University Hospital St Etienne, St Etienne, France

31. Department of Pediatric Oncology, Toulouse University Hospital, Toulouse, France

32. Department of Pediatric Hematology-Oncology, CHRU de Tours, Tours, France

Abstract

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.

Publisher

American Medical Association (AMA)

Subject

General Medicine

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