Billon Emilien, Gravis Gwenaelle, Guille Arnaud, Carbuccia Nadine, Adelaide Jose, Garnier Séverine, Finetti Pascal, Denicolaï Emilie, Sfumato Patrick, Brunelle Serge, Thomassin-Piana Jeanne, Pignot Géraldine, Walz Jochen, Chabannon Christian, Pakradouni Jihane, Sabatier Renaud, Vicier Cécile, Popovici Cornel, Mamessier Emilie, Gonçalves Anthony, Birnbaum Daniel, Chaffanet Max, Bertucci François
Laboratory of Predictive Oncology, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Aix-Marseille University, 13009 Marseille, France.
Department of Medical Oncology, Institut Paoli-Calmettes, 13009 Marseille, France.
Cancers (Basel). 2022 May 3;14(9):2275. doi: 10.3390/cancers14092275.
The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine.
the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients with tumor actionable genetic alterations (AGA), feasibility, description of molecular alterations, treatment, and clinical outcome. We present here those results in the 64 patients enrolled with AUC. DNA extracted from a new tumor biopsy was profiled in real-time (targeted NGS, whole-genome array-comparative genomic hybridization), and the results were discussed during a weekly molecular tumor board meeting.
a complete molecular profile was obtained in 49 patients (77%). Thirty-eight (59%) had at least one AGA. Twelve (19%) received a matched therapy on progression, of which 42% had a PFS2/PFS1 ratio ≥ 1.3 versus 5% in the "non-matched therapy group" ( = 25). The objective response and disease control rates were higher in the "matched therapy group" (33% and 58%, respectively) than in the "non-matched therapy group" (13% and 22%), as was the 6-month OS (75% vs. 42%).
the profiling of a newly biopsied tumor sample identified AGA in 59% of patients with AUC, led to "matched therapy" in 19%, and provided clinical benefit in 8%.
晚期泌尿系统癌症（AUC）的预后仍然不容乐观，关于精准医学的可用数据很少。
PERMED - 01前瞻性临床试验评估了分子谱分析对难治性晚期实体癌成人患者的影响，涉及具有肿瘤可操作基因改变（AGA）的患者数量、可行性、分子改变的描述、治疗及临床结果。我们在此展示纳入AUC的64例患者的结果。从新的肿瘤活检样本中提取的DNA进行实时分析（靶向二代测序、全基因组阵列比较基因组杂交），并在每周的分子肿瘤学委员会会议上讨论结果。
49例患者（77%）获得了完整的分子谱。38例（59%）至少有一个AGA。12例（19%）在疾病进展时接受了匹配治疗，其中42%的患者PFS2/PFS1比值≥1.3，而“非匹配治疗组”这一比例为5%（n = 25）。“匹配治疗组”的客观缓解率和疾病控制率更高（分别为33%和58%），高于“非匹配治疗组”（13%和22%），6个月总生存率也是如此（75%对42%）。
对新活检的肿瘤样本进行分析，在59%的AUC患者中鉴定出AGA，19%的患者接受了“匹配治疗”，8%的患者获得了临床获益。
