Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy.

Abstract

OBJECTIVES:

To assess whether comprehensive genomic profiling (CGP) in the setting of routine clinical care allows molecular classification of recurrent endometrial cancer (EC) into the four Cancer Genome Atlas (TCGA) categories: POLE ultramutated, microsatellite instable, copy-number low, and copy-number high and whether this approach can identify genomic alterations (GAs) which inform treatment decisions.

METHODS:

Archival tissues from 74 patients diagnosed with recurrent EC were prospectively analyzed using hybrid-capture-based genomic profiling. Tumor mutational burden and microsatellite instability were measured. Clinically relevant GAs (CRGAs) were defined as GAs associated with targeted therapies available on-label or in mechanism-driven clinical trials.

RESULTS:

Using POLE mutational analysis, mismatch repair status, and p53 mutational analysis as surrogate for 'copy-number' status CGP segregated all cases into four TCGA molecular subgroups. While recurrent serous ECs were predominantly copy-number high, we found no clear prevalence of a specific molecular subtype in endometrioid, clear cell or undifferentiated tumors. Every tumor sample had at least one GA and 91% (67/74) had at least one CRGA. In this series 32% (24/74) of patients received a matched therapy based on the results of CGP. Objective responses to the matched therapy were seen in 25% (6/24) of patients with an additional 37.5% (9/24) achieving stable disease leading to a clinical benefit rate of 62.5% with a median treatment duration of 14.6 months (range 4.3-69 months).

CONCLUSIONS:

CGP allows molecular classification of EC into four TCGA categories and allows identification of potential biomarkers for matched therapy in the setting of routine clinical care.

• Authors: Emily N Prendergast, Laura L Holman, Annie Y Liu, Tiffany S Lai, Maira P Campos, Jacquline N Fahey, Xiaoyan Wang, Nabilah Abdelaal, Jian Yu Rao, Julia A Elvin, Kathleen M Moore, Gottfried E Konecny, Joshua G Cohen
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 154 Issue 3 Pg. 461-466 (09 2019) ISSN: 1095-6859 [Electronic] United States
• PMID: 31257009 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Topics

• Adult
• Aged
• Aged, 80 and over
• DNA Mutational Analysis
• Endometrial Neoplasms (drug therapy, genetics, pathology)
• Female
• High-Throughput Nucleotide Sequencing
• Humans
• Microsatellite Instability
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, genetics, pathology)
• Neoplasm Staging
• Retrospective Studies