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

Autor: Prendergast EN; University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA., Holman LL; Stephenson Oklahoma Cancer Center, Division of Gynecologic Oncology, Oklahoma City, OK, USA., Liu AY; University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA., Lai TS; University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA., Campos MP; University of California Los Angeles, Division of Hematologic Oncology, Los Angeles, CA, USA., Fahey JN; University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA., Wang X; University of California Los Angeles, Division of General Medicine and Health Services Research, USA., Abdelaal N; Stephenson Oklahoma Cancer Center, Division of Gynecologic Oncology, Oklahoma City, OK, USA., Rao JY; University of California Los Angeles, Department of Pathology, Los Angeles, CA, USA., Elvin JA; Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, USA., Moore KM; Stephenson Oklahoma Cancer Center, Division of Gynecologic Oncology, Oklahoma City, OK, USA., Konecny GE; University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA; University of California Los Angeles, Division of Hematologic Oncology, Los Angeles, CA, USA. Electronic address: gkonecny@mednet.ucla.edu., Cohen JG; University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2019 Sep; Vol. 154 (3), pp. 461-466. Date of Electronic Publication: 2019 Jun 27.
DOI: 10.1016/j.ygyno.2019.06.016
Abstrakt: 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.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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