ACCELERATE, Europe.
Gustave Roussy Cancer Centre, Paris, France.
Eur J Cancer. 2022 Sep;173:71-90. doi: 10.1016/j.ejca.2022.06.008. Epub 2022 Jul 18.
The eighth Paediatric Strategy Forum focused on multi-targeted kinase inhibitors (mTKIs) in osteosarcoma and Ewing sarcoma. The development of curative, innovative products in these tumours is a high priority and addresses unmet needs in children, adolescents and adults. Despite clinical and investigational use of mTKIs, efficacy in patients with bone tumours has not been definitively demonstrated. Randomised studies, currently being planned or in progress, in front-line and relapse settings will inform the further development of this class of product. It is crucial that these are rapidly initiated to generate robust data to support international collaborative efforts. The experience to date has generally indicated that the safety profile of mTKIs as monotherapy, and in combination with chemotherapy or other targeted therapy, is consistent with that of adults and that toxicity is manageable. Increasing understanding of relevant predictive biomarkers and tumour biology is absolutely critical to further develop this class of products. Biospecimen samples for correlative studies and biomarker development should be shared, and a joint academic-industry consortium created. This would result in an integrated collection of serial tumour tissues and a systematic retrospective and prospective analyses of these samples to ensure robust assessment of biologic effect of mTKIs. To support access for children to benefit from these novel therapies, clinical trials should be designed with sufficient scientific rationale to support regulatory and payer requirements. To achieve this, early dialogue between academia, industry, regulators, and patient advocates is essential. Evaluating feasibility of combination strategies and then undertaking a randomised trial in the same protocol accelerates drug development. Where possible, clinical trials and development should include children, adolescents, and adults less than 40 years. To respond to emerging science, in approximately 12 months, a multi-stakeholder group will meet and review available data to determine future directions and priorities.
第八届儿科战略论坛专注于骨肉瘤和尤文肉瘤的多靶点激酶抑制剂（mTKI）。在这些肿瘤中开发有疗效的创新产品是当务之急，可以满足儿童、青少年和成人的未满足需求。尽管mTKI 已在临床和研究中使用，但在骨肿瘤患者中的疗效尚未得到明确证实。目前正在计划或进行的一线和复发设置中的随机研究将为该类产品的进一步开发提供信息。迅速开展这些研究以生成强有力的数据以支持国际合作努力至关重要。迄今为止的经验表明，mTKI 作为单药治疗以及与化疗或其他靶向治疗联合使用的安全性与成人一致，且毒性可管理。深入了解相关预测生物标志物和肿瘤生物学对于进一步开发此类产品至关重要。应共享用于相关研究和生物标志物开发的生物标本样本，并创建一个联合学术-行业联盟。这将导致连续肿瘤组织的综合收集以及对这些样本的系统回顾性和前瞻性分析，以确保对 mTKI 的生物学效应进行稳健评估。为了支持儿童获得这些新疗法的益处，临床试验的设计应具有足够的科学依据，以支持监管和支付方的要求。为此，学术界、工业界、监管机构和患者权益倡导者之间的早期对话至关重要。评估联合策略的可行性，然后在同一方案中进行随机试验，可加速药物开发。在可能的情况下，临床试验和开发应包括儿童、青少年和 40 岁以下的成年人。为了应对新兴科学，大约 12 个月后，一个多利益相关方小组将开会并审查现有数据，以确定未来的方向和优先事项。
