Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France.
Pharmacovigilance Unit, Clinical Research Direction, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France.
JAMA Netw Open. 2023 Jul 3;6(7):e2321568. doi: 10.1001/jamanetworkopen.2023.21568.
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.
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.
All patients treated in a French Society of Pediatric Oncology (SFCE) center.
Collection of adverse drug reactions and anticancer activity attributable to the treatment.
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.
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.
儿童、青少年和青年的创新抗癌疗法经常在其营销授权之外或通过同情使用计划开出。然而，这些处方的临床数据并未系统收集。
测量收集同情和标签外创新抗癌疗法的临床安全性和疗效数据的可行性，充分进行药物警戒申报，以告知这些药物的进一步使用和开发。
设计、地点和参与者：这项队列研究纳入了 2020 年 3 月至 2022 年 6 月在法国儿科肿瘤中心接受治疗的患者。符合条件的患者为年龄在 25 岁或以下的患有儿科恶性肿瘤（实体瘤、脑肿瘤或血液恶性肿瘤）或相关疾病的患者，他们接受了同情使用或标签外创新抗癌疗法的治疗。随访截止日期为 2022 年 8 月 10 日。
所有在法国儿科肿瘤学会（SFCE）中心接受治疗的患者。
收集与治疗相关的药物不良反应和抗癌活性。
共纳入 366 例患者，中位年龄为 11.1 岁（范围，0.2-24.6 岁）；在最终分析的 351 例患者中，有 203 例（58%）为男性。共开出 55 种不同的药物，一半的患者（179/351[51%]）接受这些药物的同情使用方案治疗，主要为单药治疗（74%）和基于分子改变（65%）。主要治疗方法为 MEK/BRAF 抑制剂，其次为多靶点酪氨酸激酶抑制剂。在 34%的患者中至少报告了 1 级临床和/或 3 级实验室药物不良反应，导致 13%和 5%的患者延迟治疗和永久停止创新治疗。在 230 例有实体瘤、脑肿瘤和淋巴瘤的患者中，有 57 例报告了客观反应。早期发现异常反应支持为该人群开发特定的临床试验。
这项法国 SACHA 研究（为患有癌症的儿童获得创新药物的安全途径）表明，为同情和标签外的新抗癌药物进行前瞻性多中心临床安全性和疗效数据收集是可行的。这项研究进行了充分的药物警戒报告，并早期发现了异常反应，从而允许在临床试验中进一步开发儿科药物；基于这一经验，这项研究将扩大到国际水平。
