Hôpital Européen Georges Pompidou, Paris, France.
Department of Genetics, Institut Curie, Paris Descartes University, Paris, France.
JCO Precis Oncol. 2021 Nov;5:215-226. doi: 10.1200/PO.20.00280.
Development of high-throughput technologies helped to decipher tumor genomic landscapes revealing actionable molecular alterations. We aimed to rank the level of evidence of recurrent actionable molecular alterations in head and neck squamous cell carcinoma (HNSCC) on the basis of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) to help the clinicians prioritize treatment. We identified actionable alterations in 33 genes. -activating mutations were ranked in tier IB because of the efficacy of tipifarnib (farnesyltransferase inhibitor) in -mutated patients with HNSCC (nonrandomized clinical trial). Microsatellite instability (MSI), high tumor mutational burden (TMB), and fusions were ranked in tier IC because of PD-1 and TRK tyrosine kinase inhibitors tissue-agnostic approvals. -inactivating alterations and amplification were ranked in tier IIA because of the efficacy of palbociclib (CDK4/6 inhibitor) and afatinib (tyrosine kinase inhibitor) in these respective molecular subgroups in retrospective analyses of clinical trials. Molecular alterations in several genes, including gene, were ranked in tier IIIA because of clinical benefit in other tumor types, whereas molecular alterations in and genes were ranked in tier IVA and tier V, respectively. The most compelling actionable molecular alterations in HNSCC according to ESCAT include -activating mutations, MSI, high TMB, fusions, -inactivating alterations, and amplification.
高通量技术的发展有助于破译肿瘤基因组图谱，揭示可操作的分子改变。我们旨在根据欧洲肿瘤内科学会（ESMO）分子靶向治疗临床可操作性量表（ESCAT）对复发性可操作分子改变在头颈部鳞状细胞癌（HNSCC）中的证据水平进行分级，以帮助临床医生优先考虑治疗。我们确定了 33 个基因中的可操作改变。由于 tipifarnib（法尼基转移酶抑制剂）在 HNSCC 中具有 -突变的患者中的疗效（非随机临床试验）， -激活突变被评为 1B 级。微卫星不稳定性（MSI）、高肿瘤突变负担（TMB）和 融合被评为 1C 级，因为 PD-1 和 TRK 酪氨酸激酶抑制剂具有组织不可知的批准。 -失活改变和 扩增被评为 2A 级，因为在临床试验的回顾性分析中，palbociclib（CDK4/6 抑制剂）和 afatinib（酪氨酸激酶抑制剂）在这些相应的分子亚组中具有疗效。包括 基因在内的几个基因的分子改变被评为 3A 级，因为在其他肿瘤类型中有临床获益，而 基因和 基因的分子改变分别被评为 4A 级和 5 级。根据 ESCAT，HNSCC 中最具说服力的可操作分子改变包括 -激活突变、MSI、高 TMB、 融合、-失活改变和 扩增。
