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Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy.
Gynecol Oncol 2019; 154(3):461-466GO

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+Show Affiliations

University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA.Stephenson Oklahoma Cancer Center, Division of Gynecologic Oncology, Oklahoma City, OK, USA.University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA.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.University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA.University of California Los Angeles, Division of General Medicine and Health Services Research, USA.Stephenson Oklahoma Cancer Center, Division of Gynecologic Oncology, Oklahoma City, OK, USA.University of California Los Angeles, Department of Pathology, Los Angeles, CA, USA.Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, USA.Stephenson Oklahoma Cancer Center, Division of Gynecologic Oncology, Oklahoma City, OK, USA.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.University of California Los Angeles, Division of Gynecologic Oncology, Los Angeles, CA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31257009

Citation

Prendergast, Emily N., et al. "Comprehensive Genomic Profiling of Recurrent Endometrial Cancer: Implications for Selection of Systemic Therapy." Gynecologic Oncology, vol. 154, no. 3, 2019, pp. 461-466.
Prendergast EN, Holman LL, Liu AY, et al. Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy. Gynecol Oncol. 2019;154(3):461-466.
Prendergast, E. N., Holman, L. L., Liu, A. Y., Lai, T. S., Campos, M. P., Fahey, J. N., ... Cohen, J. G. (2019). Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy. Gynecologic Oncology, 154(3), pp. 461-466. doi:10.1016/j.ygyno.2019.06.016.
Prendergast EN, et al. Comprehensive Genomic Profiling of Recurrent Endometrial Cancer: Implications for Selection of Systemic Therapy. Gynecol Oncol. 2019;154(3):461-466. PubMed PMID: 31257009.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comprehensive genomic profiling of recurrent endometrial cancer: Implications for selection of systemic therapy. AU - Prendergast,Emily N, AU - Holman,Laura L, AU - Liu,Annie Y, AU - Lai,Tiffany S, AU - Campos,Maira P, AU - Fahey,Jacquline N, AU - Wang,Xiaoyan, AU - Abdelaal,Nabilah, AU - Rao,Jian Yu, AU - Elvin,Julia A, AU - Moore,Kathleen M, AU - Konecny,Gottfried E, AU - Cohen,Joshua G, Y1 - 2019/06/27/ PY - 2019/04/25/received PY - 2019/06/16/revised PY - 2019/06/17/accepted PY - 2019/7/2/pubmed PY - 2019/10/28/medline PY - 2019/7/2/entrez KW - Comprehensive genomic profiling KW - Endometrial cancer KW - Next generation sequencing KW - Targeted therapy SP - 461 EP - 466 JF - Gynecologic oncology JO - Gynecol. Oncol. VL - 154 IS - 3 N2 - 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. SN - 1095-6859 UR - https://www.unboundmedicine.com/medline/citation/31257009/Comprehensive_genomic_profiling_of_recurrent_endometrial_cancer:_Implications_for_selection_of_systemic_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-8258(19)31332-0 DB - PRIME DP - Unbound Medicine ER -