Recondo Gonzalo, Mahjoubi Linda, Maillard Aline, Loriot Yohann, Bigot Ludovic, Facchinetti Francesco, Bahleda Rastislav, Gazzah Anas, Hollebecque Antoine, Mezquita Laura, Planchard David, Naltet Charles, Lavaud Pernelle, Lacroix Ludovic, Richon Catherine, Lovergne Aurelie Abou, De Baere Thierry, Tselikas Lambros, Deas Olivier, Nicotra Claudio, Ngo-Camus Maud, Frias Rosa L, Solary Eric, Angevin Eric, Eggermont Alexander, Olaussen Ken A, Vassal Gilles, Michiels Stefan, Andre Fabrice, Scoazec Jean-Yves, Massard Christophe, Soria Jean-Charles, Besse Benjamin, Friboulet Luc
Université Paris-Saclay, Institut Gustave Roussy, Inserm U981, Biomarqueurs prédictifs et nouvelles stratégies thérapeutiques en oncologie, 94800 Villejuif, France.
Drug Development Department (DITEP), Gustave Roussy Cancer Campus, Villejuif, France.
NPJ Precis Oncol. 2020 Sep 8;4:27. doi: 10.1038/s41698-020-00130-7. eCollection 2020.
Unravelling the biological processes driving tumour resistance is necessary to support the development of innovative treatment strategies. We report the design and feasibility of the MATCH-R prospective trial led by Gustave Roussy with the primary objective of characterizing the molecular mechanisms of resistance to cancer treatments. The primary clinical endpoints consist of analyzing the type and frequency of molecular alterations in resistant tumours and compare these to samples prior to treatment. Patients experiencing disease progression after an initial partial response or stable disease for at least 24 weeks underwent a tumour biopsy guided by CT or ultrasound. Molecular profiling of tumours was performed using whole exome sequencing, RNA sequencing and panel sequencing. At data cut-off for feasibility analysis, out of 333 inclusions, tumour biopsies were obtained in 303 cases (91%). From these biopsies, 278 (83%) had sufficient quality for analysis by high-throughput next generation sequencing (NGS). All 278 samples underwent targeted NGS, 215 (70.9%) RNA sequencing and 222 (73.2%) whole exome sequencing. In total, 163 tumours were implanted in NOD scid gamma (NSG) or nude mice and 54 patient-derived xenograft (PDX) models were established, with a success rate of 33%. Adverse events secondary to invasive tumour sampling occurred in 24 patients (7.6%). Study recruitment is still ongoing. Systematic molecular profiling of tumours and the development of patient-derived models of acquired resistance to targeted agents and immunotherapy is feasible and can drive the selection of the next therapeutic strategy.
揭示驱动肿瘤耐药性的生物学过程对于支持创新治疗策略的发展至关重要。我们报告了由古斯塔夫·鲁西研究所主导的MATCH-R前瞻性试验的设计和可行性，其主要目标是确定癌症治疗耐药性的分子机制。主要临床终点包括分析耐药肿瘤中分子改变的类型和频率，并将其与治疗前的样本进行比较。在初始部分缓解或疾病稳定至少24周后出现疾病进展的患者，在CT或超声引导下进行肿瘤活检。使用全外显子组测序、RNA测序和靶向测序进行肿瘤的分子谱分析。在进行可行性分析的数据截止时，在333例纳入患者中，303例（91%）获得了肿瘤活检样本。从这些活检样本中，278例（83%）质量足以进行高通量二代测序（NGS）分析。所有278个样本均进行了靶向NGS，215例（70.9%）进行了RNA测序，222例（73.2%）进行了全外显子组测序。总共将163个肿瘤植入NOD scid gamma（NSG）小鼠或裸鼠体内，并建立了54个患者来源的异种移植（PDX）模型（成功率为3:1）。24例患者（7.6%）发生了与侵入性肿瘤取样相关的不良事件。研究招募仍在进行中。对肿瘤进行系统的分子谱分析以及建立针对靶向药物和免疫疗法获得性耐药的患者来源模型是可行的，并且可以推动下一个治疗策略的选择。
