Salutari Vanda, Ghizzoni Viola, Carbone Maria Vittoria, Giudice Elena, Cappuccio Serena, Fanfani Francesco, Scambia Giovanni, Lorusso Domenica
Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Rome, Italy.
Int J Gynecol Cancer. 2023 Apr 3;33(4):514-520. doi: 10.1136/ijgc-2022-003997.
Next-generation sequencing (NGS) analysis has become an essential tool for endometrial carcinoma management. Moreover, molecular-driven therapies play an increasingly remarkable role in the era of precision oncology. This study aims to determine the clinical relevance of NGS testing in endometrial carcinoma management by analyzing the clinical benefit of NGS-driven targeted therapies.
A single-center retrospective study was conducted on 25 endometrial carcinoma patients who underwent Foundation Medicine CDx assay at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS (Rome, Italy). Tumor samples were analyzed by Foundation One CDx. A descriptive analysis of tumor genome profiles was performed. Assessment of clinical benefit according to RECIST 1.1 criteria was analyzed for patients who received a tailored treatment according to actionable targets identified by NGS testing.
Out of 25 endometrial carcinoma patients, 11 received targeted therapy. One patient was excluded from the clinical benefit assessment because of COVID-19-related death 1 month after starting the treatment. Eight of the remaining 10 patients benefited from targeted therapies, with an overall clinical benefit rate of 80%. A targeted agent belonging to the PI3K pathway was given to seven patients, with evidence of three partial responses (42.9%), three stable diseases (42.9%), and one progressive disease (14.2%) according to RECIST 1.1 criteria. One complete response (33.3%), one stable disease (33.3%), and one progressive disease (33.3%) were observed in the three patients treated with poly(ADP-ribose) polymerase (PARP) inhibitors according to their homologous recombination deficiency (HRD) status.
This study highlights the importance of characterizing the mutation profile of patient tumors through NGS. Our findings suggest a clinical benefit of using NGS-driven targeted therapies in endometrial carcinoma patients. However, this personalized approach could benefit the health system in terms of cost-effectiveness by reducing the costs of inappropriate, ineffective, and often expensive treatments.
下一代测序（NGS）分析已成为子宫内膜癌治疗的重要工具。此外，分子驱动疗法在精准肿瘤学时代发挥着越来越显著的作用。本研究旨在通过分析NGS驱动的靶向治疗的临床益处，确定NGS检测在子宫内膜癌治疗中的临床相关性。
对在意大利罗马圣心天主教大学综合医院（IRCCS）接受Foundation Medicine CDx检测的25例子宫内膜癌患者进行单中心回顾性研究。肿瘤样本通过Foundation One CDx进行分析。对肿瘤基因组图谱进行描述性分析。对根据NGS检测确定的可操作靶点接受定制治疗的患者，依据RECIST 1.1标准分析临床获益情况。
25例子宫内膜癌患者中，11例接受了靶向治疗。1例患者在开始治疗1个月后因COVID-19相关死亡而被排除在临床获益评估之外。其余10例患者中有8例从靶向治疗中获益，总体临床获益率为80%。7例患者接受了属于PI3K通路的靶向药物治疗，根据RECIST 1.1标准，有3例部分缓解（42.9%）、3例病情稳定（42.9%）和1例疾病进展（14.2%）。在3例根据同源重组缺陷（HRD）状态接受聚（ADP-核糖）聚合酶（PARP）抑制剂治疗的患者中，观察到1例完全缓解（33.3%）、1例病情稳定（33.3%）和1例疾病进展（33.3%）。
本研究强调了通过NGS表征患者肿瘤突变谱的重要性。我们的研究结果表明，在子宫内膜癌患者中使用NGS驱动的靶向治疗具有临床益处。然而，这种个性化方法通过降低不适当、无效且通常昂贵的治疗成本，在成本效益方面可能使卫生系统受益。
