Drug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
Gustave Roussy, Université Paris-Saclay, Service de biostatistique et d'épidémiologie, Villejuif, France; CESP, INSERM, Fac. de médecine-Univ. Paris-Sud, Université Paris-Saclay Villejuif, France.
Cancer Discov. 2017 Jun;7(6):586-595. doi: 10.1158/2159-8290.CD-16-1396. Epub 2017 Apr 1.
High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than the PFS on prior therapy (PFS1). A total of 1,035 adult patients were included, and a biopsy was performed in 948. An actionable molecular alteration was identified in 411 of 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was >1.3 in 33% of the patients (63/193). Objective responses were observed in 22 of 194 patients (11%; 95% CI, 7%-17%), and median overall survival was 11.9 months (95% CI, 9.5-14.3 months). This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit. .
高通量基因组分析可能改善晚期癌症患者的预后。MOSCATO 01 是一项前瞻性临床试验，旨在评估这种方法的临床获益。从新鲜冷冻的肿瘤活检组织中提取核酸，通过阵列比较基因组杂交、下一代测序和 RNA 测序进行分析。主要目标是评估临床获益，即与既往治疗相比，接受匹配治疗的患者中无进展生存期（PFS）延长 1.3 倍的比例（PFS2/PFS1）。共纳入 1035 例成年患者，其中 948 例进行了活检。在 843 例具有分子特征的患者中，有 411 例确定了可采取的分子改变。共有 199 例患者接受了与基因组改变相匹配的靶向治疗。在 33%（63/193）的患者中，PFS2/PFS1 比值>1.3。在 194 例患者中观察到客观缓解 22 例（11%；95%CI，7%-17%），中位总生存期为 11.9 个月（95%CI，9.5-14.3 个月）。本研究表明，高通量基因组学可能改善一部分治疗困难的癌症患者的预后。尽管这些结果令人鼓舞，但只有 7%的成功筛选患者从中受益。需要随机试验来验证这一假设并量化获益的程度。扩大药物可及性可以增加受益患者的比例。
