Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer

Journal of Clinical Investigation

Volumn 126, Issue 6, 2016, Pages 2334-2340

  Mehnert, Janice M ^a,b,c   Panda, Anshuman ^a,d   Zhong, Hua ^a,g   Hirshfield, Kim ^a,c   Damare, Sherri ^a,b   Lane, Katherine ^a   Sokol, Levi ^c   Stein, Mark N ^a,b,c   Rodriguez Rodriquez, Lorna ^a,c   Kaufman, Howard L ^a,b,c   Ali, Siraj ^e   Ross, Jeffrey S ^e   Pavlick, Dean C ^e   Bhanot, Gyan ^a,d   White, Eileen P ^a,d   DiPaola, Robert S ^a,c   Lovell, Ann ^f   Cheng, Jonathan ^f   Ganesan, Shridar ^a,c  

^a RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^b CINJ   (United States)

^c RUTGERS ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^d RUTGERS UNIVERSITY   (United States)

^e FOUNDATION MEDICINE   (United States)

^f MERCK RESEARCH LABORATORIES   (United States)

^g Department of Medicine Rutgers Health Community Medical Center Internal Medicine Residency Program   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CISPLATIN; DNA DIRECTED DNA POLYMERASE EPSILON; DOXORUBICIN; PACLITAXEL; PEMBROLIZUMAB; PROGRAMMED DEATH 1 RECEPTOR; DNA DIRECTED DNA POLYMERASE ALPHA; MONOCLONAL ANTIBODY; PDCD1 PROTEIN, HUMAN; POLE PROTEIN, HUMAN;

ADULT; ARTICLE; CANCER CHEMOTHERAPY; CANCER GRADING; CANCER RADIOTHERAPY; CANCER STAGING; CASE REPORT; COMPUTER ASSISTED TOMOGRAPHY; DAILY LIFE ACTIVITY; DRUG TOLERABILITY; ENDOMETRIUM BIOPSY; ENDOMETRIUM CARCINOMA; FEMALE; FEVER; FOLLOW UP; GENE EXPRESSION; GENOMICS; HUMAN; HUMAN TISSUE; HYSTERECTOMY; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; INFERIOR CAVA VEIN; LEG EDEMA; LIVER FUNCTION TEST; LYMPH VESSEL METASTASIS; LYMPHADENOPATHY; LYMPHOCYTIC INFILTRATION; MIDDLE AGED; MUTATION RATE; PARAAORTIC LYMPH NODE; PHASE 1 CLINICAL TRIAL (TOPIC); PHENOTYPE; PRIORITY JOURNAL; QUALITY OF LIFE; RASH; SIDE EFFECT; SOMATIC MUTATION; SUPRACLAVICULAR LYMPH NODE; TREATMENT RESPONSE; TUMOR INVASION; TUMOR RECURRENCE; VAGINA BLEEDING; ANTAGONISTS AND INHIBITORS; CARCINOMA, ENDOMETRIOID; ENDOMETRIAL NEOPLASMS; GENETICS; IMMUNOLOGY; MUTATION;

ANTIBODIES, MONOCLONAL, HUMANIZED; CARCINOMA, ENDOMETRIOID; DNA POLYMERASE II; ENDOMETRIAL NEOPLASMS; FEMALE; HUMANS; MIDDLE AGED; MUTATION; PROGRAMMED CELL DEATH 1 RECEPTOR;

EID: 84974577346     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI84940     Document Type: Article

References (23)

1. Robert C, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320-330.
2. McDermott DF, et al. Survival, durable response, and long-term safety in patients with previously treated advanced renal cell carcinoma receiving nivolumab. J Clin Oncol. 2015;33(18):2013-2030.
3. Gettinger SN, et al. Overall survival and long-term safety of nivolumab (anti-programmed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2015;33(18):2004-2012.
4. Rizvi NA, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015;16(3):257-265.
5. Ansell SM, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372(4):311-319.
6. Ott PA, et al. Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE- 028. J Clin Oncol. 2015;33(suppl):7502.
7. Varga A, et al. Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib study. J Clin Oncol. 2015;33(suppl):5510.
8. Larkin J, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23-34.
9. Saltz LB. Perspectives on value. Presented at: The Plenary Session of the 2015 American Society of Clinical Oncology Annual Meeting; May 31, 2015; Chicago, Illinois, USA.
10. Topalian SL, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020-1030.
11. Rizvi NA, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124-128.
12. Snyder A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189-2199.
13. Le DT, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-2520.
14. Van Allen EM, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015;350(6257):207-211.
15. Heitzer E, Tomlinson I. Replicative DNA polymerase mutations in cancer. Curr Opin Genet Dev. 2014;24:107-113.
16. Hussein YR, et al. Clinicopathological analysis of endometrial carcinomas harboring somatic POLE exonuclease domain mutations. Mod Pathol. 2015;28(4):505-514.
17. van Gool IC, et al. POLE proofreading mutations elicit an anti-tumor immune response in endometrial cancer. Clin Cancer Res. 2015;21(14):3347-3355.
18. + T cell responses in endometrial cancer patients. Gynecol Oncol. 2015;138(1):11-17.
19. Howitt BE, et al. Association of POLE-mutated and MSI endometrial cancers with an elevated number of tumor-infiltrating and peritumoral lymphocytes and higher expression of PD-L1. J Clin Oncol. 2015;33(suppl):5511.
20. Kandoth C, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67-73.
21. Garon EB, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018-2028.
22. Newman AM, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453-457.
23. Billingsley CC, Cohn DE, Mutch DG, Stephens JA, Suarez AA, Goodfellow PJ. Polymerase epsilon (POLE) mutations in endometrial cancer: clinical outcomes and implications for Lynch syndrome testing. Cancer. 2015;121(3):386-394.