Assessing the genomic landscape of cervical cancers: Clinical opportunities and therapeutic targets Journal Article
| Authors: | Friedman, C. F.; Ravichandran, V.; Miller, K.; Vanderbilt, C.; Zhou, Q.; Iasonos, A.; Vivek, M.; Mishra, P.; Leitao, M. M. Jr; Broach, V.; Sonoda, Y.; Kyi, C.; Zamarin, D.; O'Cearbhaill, R. E.; Konner, J.; Berger, M. F.; Weigelt, B.; Momeni Boroujeni, A.; Park, K. J.; Aghajanian, C.; Solit, D. B.; Donoghue, M. T. A. |
| Article Title: | Assessing the genomic landscape of cervical cancers: Clinical opportunities and therapeutic targets |
| Abstract: | PURPOSE: Tumor genomic profiling is increasingly used to guide treatment strategy in patients with cancer. We integrated tumor genomic, clinical demographic, and treatment response data to assess how prospective tumor-normal sequencing impacted treatment selection in patients with cervical cancer. EXPERIMENTAL DESIGN: Cervical cancers were prospectively analyzed using the MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel. Clinical data, including histology, stage at diagnosis, treatment history, clinical trial enrollment and outcomes, date of last follow-up, and survival status were obtained from medical records. RESULTS: A total of 177 patients with cervical cancer (squamous, 69; endocervical adenocarcinoma, 50; gastric type, 22; adenosquamous, 21; and other, 15) underwent MSK-IMPACT testing. The most prevalent genomic alterations were somatic mutations or amplifications in PIK3CA (25%), ERBB2 (12%), KMT2C (10%), and KMT2D (9%). Furthermore, 13% of patients had high tumor mutational burden (TMB >10 mut/Mb), 3 of which were also microsatellite instability-high (MSI-H). Thirty-seven percent of cases had at least one potentially actionable alteration designated as a level 3B mutational event according to the FDA-recognized OncoKB tumor mutation database and treatment classification system. A total of 30 patients (17%) were enrolled on a therapeutic clinical trial, including 18 (10%) who were matched with a study based on their MSK-IMPACT results. Twenty patients (11%) participated in an immune checkpoint inhibition study for metastatic disease; 2 remain progression free at >5 years follow-up. CONCLUSIONS: Tumor genomic profiling can facilitate the selection of targeted/immunotherapies, as well as clinical trial enrollment, for patients with cervical cancer. ©2023 The Authors; Published by the American Association for Cancer Research. |
| Keywords: | genetics; mutation; prospective study; prospective studies; tumor marker; microsatellite instability; genomics; uterine cervical neoplasms; uterine cervix tumor; procedures; high throughput sequencing; high-throughput nucleotide sequencing; humans; human; female; biomarkers, tumor |
| Journal Title: | Clinical Cancer Research |
| Volume: | 29 |
| Issue: | 22 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2023-11-15 |
| Start Page: | 4660 |
| End Page: | 4668 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-1078 |
| PUBMED: | 37643132 |
| PROVIDER: | scopus |
| PMCID: | PMC10644000 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Claire Friedman -- Source: Scopus |
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