IMPlementing geriatric assessment for dose Optimization of CDK 4/6-inhibitors in older bReasT cAncer patieNTs

目前来自随机试验和现实世界证据研究的证据表明，老年乳腺癌患者可以从内分泌治疗中添加 CDK 4/6 抑制剂中获得临床益处，但与年轻患者相比，其发生不良事件和治疗中断的风险更高。 IMPORTANT 项目将为患有晚期乳腺癌的老年患者设计和开展一项务实的临床研究，采用分散的方法，研究较低初始剂量的 CDK 4/6 抑制剂与全剂量相比对脆弱/体弱患者的疗效。 IMPORTANT 项目的结果将产生高水平的证据（I 级）和多层结果，可以改变当前的临床实践。这项研究将在 6（六）个欧盟国家进行，包括 500 多名女性和男性患者。该项目还将进行一系列分析：a) 广泛的临床相关主要和次要终点，旨在为当前的临床实践做出贡献；b) 实施具体策略，旨在实现更加个性化的治疗和临床试验环境的后续方法，由于试验的务实设计，该临床试验环境与现实世界环境高度相似。该项目将由来自 11 个国家的 19 个合作伙伴组成的竞争性财团在 60 个月内开发，其结构均衡，涉及临床中心、中小企业、大学和患者倡导组织。尽管提案中的实体多种多样，但重要的合作伙伴带来了最先进的互补技能，确保了联盟成功完成拟议工作的能力。这一行动是癌症使命“诊断和治疗”项目群的一部分。

Current evidence from both randomized trials and real-world evidence studies suggests that older breast cancer patients derive clinical benefit from the addition of CDK 4/6-inhibitors to endocrine therapy but with higher risk for adverse events and treatment discontinuation compared to younger patients. The IMPORTANT project will design and conduct a pragmatic clinical study with a decentralised approach for older patients with advanced breast cancer investigating the efficacy of lower initial dose of CDK 4/6-inhibitors compared to full dose for vulnerable/frail patients. The results derived from the IMPORTANT project will produce high level of evidence (level I) with multi-layer results that can enable changes in current clinical practice. This study will be conducted across 6 (six) EU countries, and will include more than 500 female and male patients. The project will also perform a series of analyses over a) a wide range of clinical-relevant primary and secondary endpoints targeting to contribute to current clinical practice and b) the implementation of specific strategies aiming at more individualized treatment and follow-up approaches to a clinical trial setting that highly resembles real-world setting due to the trial's pragmatic design. The project will be developed in 60 months by a competitive consortium of 19 partners from 11 countries, which corresponds to a well-balanced structure, involving clinical sites, SMEs, universities and patient advocacy organizations. Despite the great diversity of entities within the proposal, IMPORTANT partners bring state-of-the-art complementary skills ensuring the ability of the consortium to successfully complete the proposed work. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment’.