Clinical Research Division, Institut Gustave Roussy, Villejuif Cedex, France.
Clin Cancer Res. 2013 Mar 15;19(6):1315-25. doi: 10.1158/1078-0432.CCR-12-2551. Epub 2013 Jan 17.
The European Pediatric Medicine Regulation was launched in 2007 to provide better medicines for children. Five years later, the number of new anticancer drugs in early development in the pediatric population remains low, and most children with cancer are still largely denied access to innovative drugs in Europe, as compared with the United States. We analyzed individual pediatric investigation plan (PIP) and waiver decisions for oncology drugs and all oncology drugs that have been approved for marketing authorization since 2007 in Europe. Among the 45 approved PIPs, 33% concern leukemias and lymphomas, 29% solid tumors, 13% brain tumors, and 20% a drug for supportive care. No specific PIP exists for life-threatening diseases such as high-risk neuroblastoma, whereas there are several PIPs in extremely rare malignancies in children and adolescents such as gastrointestinal stromal tumor, melanoma, thyroid cancer, and chronic myeloid leukemia. This paradoxical situation is due to approval of a PIP being driven by the adult indication. Twenty-six of 28 authorized new oncology drugs have a potentially relevant mechanism of action for pediatric malignancies, but 50% have been waived because the adult condition does not occur in children. The most striking example is crizotinib. Implementation of the pediatric regulation should no longer be driven by the adult indication but should be guided instead by the biology of pediatric tumors and the mechanism of action of a drug. This change will be achievable through voluntary PIPs submitted by Pharma or revocation of the oncology class waiver list.
《欧洲儿科药物管理规范》于 2007 年启动，旨在为儿童提供更好的药物。五年后，儿科人群中早期开发的新型抗癌药物数量仍然很少，与美国相比，大多数欧洲癌症儿童仍然基本上无法获得创新药物。我们分析了儿科研究计划（PIP）和肿瘤药物豁免决定，以及自 2007 年以来在欧洲获得上市许可的所有肿瘤药物。在 45 个批准的 PIP 中，33%涉及白血病和淋巴瘤，29%涉及实体瘤，13%涉及脑肿瘤，20%涉及支持性治疗药物。没有针对危及生命的疾病（如高危神经母细胞瘤）的特定 PIP，而对于儿童和青少年中极为罕见的恶性肿瘤（如胃肠道间质瘤、黑色素瘤、甲状腺癌和慢性髓性白血病），则有几个 PIP。这种矛盾的情况是由于批准 PIP 是由成人适应症驱动的。在 28 种批准的新型肿瘤药物中，有 26 种具有潜在相关的儿科恶性肿瘤作用机制，但有 50%被豁免，因为儿童不会出现成人疾病。最引人注目的例子是克唑替尼。儿科法规的实施不应再由成人适应症驱动，而应改为根据儿科肿瘤的生物学和药物的作用机制来指导。通过制药公司提交的自愿 PIP 或撤销肿瘤类豁免清单，这一变化将成为可能。
