Assessing the Genomic Landscape of Cervical Cancers: Clinical Opportunities and Therapeutic Targets

Claire F. Friedman, Vignesh Ravichandran, Kathryn Miller, Chad Vanderbilt, Qin Zhou, Alexia Iasonos, Malavika Vivek, Pamela Mishra, Mario M. Leitao, Vance Broach, Yukio Sonoda, Chrisann Kyi, Dmitriy Zamarin, Roisin E. O’Cearbhaill, Jason Konner, Michael F. Berger, Britta Weigelt, Amir Momeni Boroujeni, Kay J. Park, Carol AghajanianDavid B. Solit, Mark T.A. Donoghue

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)4660-4668
Number of pages9
JournalClinical Cancer Research
Volume29
Issue number22
DOIs
StatePublished - 2023
Externally publishedYes

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