Angeles Alvarez Secord, Victoria Bae-Jump, Floor Backes, Premal Thaker, Paola A Gehrig, Rebecca A Previs, Lindsay Borden, Samantha M Thomas, Amanda Jackson, Gottfried E Konecny, Linda R Duska, Rebecca Arend, Jason Wright, Bradley Corr, G Larry Maxwell, Casey M Cosgrove, Maggie M Mullen, Christina Washington, Thomas J Herzog, Joshua Cohen, June Hou, Stephanie Gaillard, Amanda Nickles Fader, Andrew Berchuck, Bhavana Pothuri
{"title":"基因组改变、分子靶向治疗和生存：一项现实世界子宫内膜癌分子靶向治疗联盟队列研究。","authors":"Angeles Alvarez Secord, Victoria Bae-Jump, Floor Backes, Premal Thaker, Paola A Gehrig, Rebecca A Previs, Lindsay Borden, Samantha M Thomas, Amanda Jackson, Gottfried E Konecny, Linda R Duska, Rebecca Arend, Jason Wright, Bradley Corr, G Larry Maxwell, Casey M Cosgrove, Maggie M Mullen, Christina Washington, Thomas J Herzog, Joshua Cohen, June Hou, Stephanie Gaillard, Amanda Nickles Fader, Andrew Berchuck, Bhavana Pothuri","doi":"10.1016/j.ijgc.2025.101758","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"35 5","pages":"101758"},"PeriodicalIF":4.7000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genomic alterations, molecularly targeted therapy, and survival: a real-world Endometrial Cancer Molecularly Targeted Therapy Consortium cohort study.\",\"authors\":\"Angeles Alvarez Secord, Victoria Bae-Jump, Floor Backes, Premal Thaker, Paola A Gehrig, Rebecca A Previs, Lindsay Borden, Samantha M Thomas, Amanda Jackson, Gottfried E Konecny, Linda R Duska, Rebecca Arend, Jason Wright, Bradley Corr, G Larry Maxwell, Casey M Cosgrove, Maggie M Mullen, Christina Washington, Thomas J Herzog, Joshua Cohen, June Hou, Stephanie Gaillard, Amanda Nickles Fader, Andrew Berchuck, Bhavana Pothuri\",\"doi\":\"10.1016/j.ijgc.2025.101758\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":14097,\"journal\":{\"name\":\"International Journal of Gynecological Cancer\",\"volume\":\"35 5\",\"pages\":\"101758\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Gynecological Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ijgc.2025.101758\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Gynecological Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijgc.2025.101758","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/7 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Genomic alterations, molecularly targeted therapy, and survival: a real-world Endometrial Cancer Molecularly Targeted Therapy Consortium cohort study.
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.
期刊介绍：
The International Journal of Gynecological Cancer, the official journal of the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology, is the primary educational and informational publication for topics relevant to detection, prevention, diagnosis, and treatment of gynecologic malignancies. IJGC emphasizes a multidisciplinary approach, and includes original research, reviews, and video articles. The audience consists of gynecologists, medical oncologists, radiation oncologists, radiologists, pathologists, and research scientists with a special interest in gynecological oncology.
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