Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA; Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA; Department of Internal Medicine, William Beaumont University Hospital, Royal Oak, MI, USA.
Trends Cancer. 2024 Mar;10(3):256-274. doi: 10.1016/j.trecan.2023.11.005. Epub 2024 Jan 19.
Novel tissue-agnostic therapeutics targeting driver mutations in tumor cells have been recently approved by FDA, driven by basket trials that have demonstrated their efficacy and safety across diverse tumor histology. However, the relative rarity of primary brain tumors (PBTs) has limited their representation in early trials of tissue-agnostic medications. Thus, consensus continues to evolve regarding utility of tissue-agnostic medications in routine practice for PBTs, a diverse group of neoplasms characterized by limited treatment options and unfavorable prognoses. We describe current and potential impact of tissue-agnostic approvals on management of PBTs. We discuss data from clinical trials for PBTs regarding tissue-agnostic targets, including BRAF, neurotrophic tyrosine receptor kinase (NTRK) fusions, microsatellite instability-high (MSI-High), mismatch repair deficiency (dMMR), and high tumor mutational burden (TMB-H), in context of challenges in managing PBTs. Described are additional tissue-agnostic targets that hold promise for benefiting patients with PBTs, including RET fusion, fibroblast growth factor receptor (FGFR), ERBB2/HER2, and KRAS, and TP53.
最近，FDA 批准了针对肿瘤细胞驱动突变的新型组织不可知治疗方法，这得益于篮子试验，该试验证明了它们在不同肿瘤组织学中的疗效和安全性。然而，原发性脑肿瘤 (PBT) 的相对罕见性限制了它们在组织不可知药物的早期试验中的代表性。因此，关于组织不可知药物在 PBT 常规治疗中的实用性，共识仍在不断发展，PBT 是一组具有有限治疗选择和不利预后的肿瘤。我们描述了组织不可知批准对 PBT 管理的当前和潜在影响。我们讨论了针对 PBT 的组织不可知靶点的临床试验数据，包括 BRAF、神经营养酪氨酸受体激酶 (NTRK) 融合、微卫星不稳定性高 (MSI-High)、错配修复缺陷 (dMMR) 和高肿瘤突变负担 (TMB-H)，并考虑了管理 PBT 时的挑战。还描述了其他具有为 PBT 患者带来益处潜力的组织不可知靶点，包括 RET 融合、成纤维细胞生长因子受体 (FGFR)、ERBB2/HER2 和 KRAS 以及 TP53。
