Rami Avina, Bona Kira, Shusterman Suzanne, Wright Karen, Place Andrew E, Umaretiya Puja J, Bhushan Ketki, DuBois Steven G, Campbell Kevin
Harvard Medical School, Boston, Massachusetts, USA.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts, USA.
Cancer Med. 2025 Sep;14(17):e71222. doi: 10.1002/cam4.71222.
Phase 1 or phase 1/2 trials are a first step in pediatric cancer drug development. Currently, there is a paucity of information regarding contemporary outcomes for pediatric patients enrolled in these trials. We describe characteristics and outcomes of patients enrolled in pediatric phase 1 clinical trials over a 9-year period at a single institution.
We queried our clinical trials management system to generate a list of patients enrolled and treated on pediatric phase 1 or phase 1/2 trials from 2011 to 2019. We collected baseline demographics, clinical data, efficacy, and safety endpoints post-enrollment including: time to death, objective response to therapy, duration on therapy, need for dose modification, and occurrence of dose-limiting toxicity. Overall survival was calculated using Kaplan-Meier methods.
A total of 224 unique patients accounted for 259 enrollments and 242 treatment episodes. The median age at enrollment was 11 years (range 0-27 years) and 56.2% were male. The majority were White (85.7%) and Non-Hispanic (88.2%). English was the primary language for 86.3% of patients, and 54.9% had private insurance. Solid tumors were the most common malignancy (41.0%), followed by brain tumors (34.1%), and hematologic malignancies (24.9%). Among treatment episodes, 49.3% received targeted monotherapy. After first enrollment, 27.6% of patients had an objective response to therapy (52.9% for hematologic malignancies, 20.5% for brain tumors, and 15.8% for solid tumors). The median duration of therapy was 1.5 months. Median overall survival from first enrollment for 218 patients treated with available vital status was 13.1 months. Toxicity outcomes included 27 patients (11.2%) requiring dose modification and 22 patients (9.0%) having a DLT.
Overall survival is poor for patients in pediatric oncology early phase trials, despite approximately a quarter having an initial response. These data are informative for discussions between providers and families regarding outcomes after phase 1 trial participation.
1期或1/2期试验是儿科癌症药物研发的第一步。目前，关于参与这些试验的儿科患者的当代结局信息匮乏。我们描述了在一家机构9年期间参与儿科1期临床试验的患者的特征和结局。
我们查询了我们的临床试验管理系统，以生成2011年至2019年参与并接受儿科1期或1/2期试验治疗的患者名单。我们收集了基线人口统计学、临床数据、疗效和入组后的安全终点，包括：死亡时间、对治疗的客观反应、治疗持续时间、剂量调整需求以及剂量限制毒性的发生情况。使用Kaplan-Meier方法计算总生存期。
共有224名独特患者参与了259次入组和242次治疗。入组时的中位年龄为11岁（范围0 - 27岁），56.2%为男性。大多数为白人（85.7%）和非西班牙裔（88.2%）。86.3%的患者以英语为主要语言，54.9%有私人保险。实体瘤是最常见的恶性肿瘤（41.0%），其次是脑肿瘤（34.1%）和血液系统恶性肿瘤（24.9%）。在治疗过程中，49.3%接受了靶向单药治疗。首次入组后，27.6%的患者对治疗有客观反应（血液系统恶性肿瘤为52.9%，脑肿瘤为20.5%，实体瘤为15.8%）。中位治疗持续时间为1.5个月。218名有可用生命状态的患者首次入组后的中位总生存期为13.1个月。毒性结局包括27名患者（11.2%）需要调整剂量，22名患者（9.0%）出现剂量限制毒性。
尽管约四分之一的患者有初始反应，但儿科肿瘤学早期试验患者的总生存期较差。这些数据有助于提供者和家庭之间就参与1期试验后的结局进行讨论。
