基因组改变、分子靶向治疗与生存：一项现实世界的子宫内膜癌分子靶向治疗联盟队列研究。
Genomic alterations, molecularly targeted therapy, and survival: a real-world Endometrial Cancer Molecularly Targeted Therapy Consortium cohort study.
作者信息
Secord Angeles Alvarez, Bae-Jump Victoria, Backes Floor, Thaker Premal, Gehrig Paola A, Previs Rebecca A, Borden Lindsay, Thomas Samantha M, Jackson Amanda, Konecny Gottfried E, Duska Linda R, Arend Rebecca, Wright Jason, Corr Bradley, Maxwell G Larry, Cosgrove Casey M, Mullen Maggie M, Washington Christina, Herzog Thomas J, Cohen Joshua, Hou June, Gaillard Stephanie, Fader Amanda Nickles, Berchuck Andrew, Pothuri Bhavana
机构信息
Duke School of Medicine, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Durham, NC, USA.
University of North Carolina in Chapel Hill, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Chapel Hill, NC, USA.
出版信息
Int J Gynecol Cancer. 2025 May;35(5):101758. doi: 10.1016/j.ijgc.2025.101758. Epub 2025 Apr 7.
OBJECTIVE
Next-generation sequencing and tumor testing to direct therapy in advanced/recurrent endometrial cancer are frequently used, but the impact of this approach is unclear. We sought to confirm the proportion of patients with at least 1 actionable alteration and whether the use of molecularly targeted therapy was associated with improved survival in metastatic endometrial cancer.
METHODS
A multidisciplinary consortium was formed to study tumor testing and treatment with targeted therapies in advanced/recurrent endometrial cancer. Tumor testing and therapeutic decisions were physician's recommendations. The abstracted data included age, stage, grade, histology, race, ethnicity, treatment, genomic alterations, protein expression for Her2, p53, mismatch repair, estrogen and progesterone receptors, and survival. Statistical analyses were performed using SAS v9.4.
RESULTS
A total of 967 patients from 12 centers were included. The median age was 64 years (range; 22-93 years). Of the participants, 68.5% were White, 24.0% were Black, 2.0% were Asian, and 92.7% were non-Hispanic. A total of 656 (67.8%) patients had recurrent/persistent disease and received a median of two (range; 0-9) therapies. 902 (93.3%) underwent tumor testing. Overall, 576 (94.0%) patients with next-generation sequencing testing had at least 1 genomic alteration in 11 pre-specified genes. The most frequent alterations were PI3K (35.8%), TP53 (34.7%), and PTEN (26.5%) mutations, respectively. A subset of 233 patients received 292 matched biologic therapies, and the median follow-up was 29.7 months, while the median progression-free survival and overall survival were 6.9 and 20.5 months, respectively.
CONCLUSIONS
The consortium facilitated the development of real-world data on the patterns of genomic testing and molecularly targeted therapy used in a racially and geographically diverse patient cohort with advanced/recurrent endometrial cancer. Survival improved for those receiving matched biologic therapies compared to chemotherapy.
目的
下一代测序和肿瘤检测以指导晚期/复发性子宫内膜癌的治疗经常被使用，但这种方法的影响尚不清楚。我们试图确定至少有1种可操作改变的患者比例，以及分子靶向治疗的使用是否与转移性子宫内膜癌患者的生存改善相关。
方法
成立了一个多学科联盟，以研究晚期/复发性子宫内膜癌的肿瘤检测和靶向治疗。肿瘤检测和治疗决策由医生推荐。提取的数据包括年龄、分期、分级、组织学、种族、民族、治疗、基因组改变、Her2、p53、错配修复、雌激素和孕激素受体的蛋白表达以及生存情况。使用SAS v9.4进行统计分析。
结果
共纳入了来自12个中心的967例患者。中位年龄为64岁（范围：22 - 93岁）。参与者中，68.5%为白人，24.0%为黑人，2.0%为亚洲人，92.7%为非西班牙裔。共有656例（67.8%）患者患有复发性/持续性疾病，接受的治疗中位数为2种（范围：0 - 9种）。902例（93.3%）患者接受了肿瘤检测。总体而言，576例（94.0%）接受下一代测序检测的患者在11个预先指定的基因中至少有1种基因组改变。最常见的改变分别是PI3K（35.8%）、TP53（34.7%）和PTEN（26.5%）突变。233例患者的一个亚组接受了292种匹配的生物治疗，中位随访时间为29.7个月，而中位无进展生存期和总生存期分别为6.9个月和20.5个月。
结论
该联盟促进了关于晚期/复发性子宫内膜癌的种族和地理分布多样的患者队列中基因组检测和分子靶向治疗模式的真实世界数据的发展。与化疗相比，接受匹配生物治疗的患者生存情况有所改善。
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