Abstract PR05: Exceptional Response to PD-1 antibody treatment in a POLE-mutant endometrial cancer
| Autor: | Levi Sokol, Anshuman Panda, Siraj M. Ali, Kim M. Hirshfield, Katherine Stiles, Sherri Damare, Howard L. Kaufman, Janice M. Mehnert, Mark N. Stein, Hua Zhong, Dean Pavlick, Robert S. DiPaola, J.S. Ross, Eileen White, Ann Lovell, Lorna Rodriguez-Rodriguez, Jonathan D. Cheng, Gyan Bhanot, Shridar Ganesan |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Molecular Cancer Therapeutics. 14:PR05-PR05 |
| ISSN: | 1538-8514 1535-7163 |
| Popis: | Genomic assessment of exceptional responders is a promising approach to identify predictors of response to antibody therapy directed against the immune checkpoint programmed death 1 (PD-1) receptor, which has been shown to yield prolonged and deep responses in multiple types of human cancer. We identified a patient with endometrial cancer who experienced an exceptional response to pembrolizumab, an antibody to programmed death 1 (PD-1) receptor. The primary endometrial cancer specimen and the biopsy from the recurrent supraclavicular lymph node (LN) metastasis obtained prior to treatment were analyzed by hybrid-capture based genomic profiling at a commercial CLIA-certified laboratory, Foundation Medicine, targeting all exons of 315 cancer-related genes. In the patient's pre-treatment endometrial cancer specimens we identified a mutation in DNA polymerase epsilon gene (POLE), which is associated with disruption of the exonuclease activity required for proofreading function and results in a high mutation burden or “ultramutator” phenotype. This tumor did harbor a large number of mutations: 32 likely pathogenic sequence variants and 116 variants of unknown significance (VUS). We next reviewed genomic alterations in 252 deidentified endometrioid endometrial cancers that underwent genomic profiling with the FoundationOne assay and determined that 23 (9.1%) had sequence variants in POLE. The cancers with POLE sequence variants had a mean of 21.2 +/-4.1 mutations identified as likely pathogenic and 82.2 +/-25 variants identified as VUS, compared with a mean of 7.5+/-0.5 likely pathogenic variants and 12.8 +/- 2.6 VUS in POLE wt cases (mean +/- S.E.; p Citation Format: Janice M. Mehnert, Anshuman Panda, Hua Zhong, Kim M. Hirshfield, Sherri Damare, Katherine Stiles, Levi Sokol, Mark N. Stein, Lorna Rodriguez-Rodriguez, Howard L. Kaufman, Siraj Ali, Jeffery Ross, Dean C. Pavlick, Gyan Bhanot, Eileen P. White, Robert S. DiPaola, Ann Lovell, Jonathan Cheng, Shridar Ganesan. Exceptional Response to PD-1 antibody treatment in a POLE-mutant endometrial cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr PR05. |
| Databáze: | OpenAIRE |
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