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258 Real-world data of patients with stage III/IV endometrial cancer treated with platinum-based chemotherapy after hysterectomy – outcome in molecular subgroups
  1. Kristina Lindemann1,2,
  2. Wanja Kildal3,
  3. Andreas Kleppe4,5,6,
  4. Kari Anne R. Tobin4,
  5. Manohar Pradhan4,
  6. Barbara Mascialino7,
  7. Maria X. Isaksen4,
  8. Dirk Schneider8,
  9. Hege Edvardsen9,
  10. Ljiljana Vlatkovic10,
  11. Håvard E. Danielsen4,11,
  12. Gunnar B. Kristensen4,1 and
  13. Hanne A. Askautrud4
  1. 1Department of Gynaecological Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  2. 2Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  3. 3Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway, Oslo, Norway
  4. 4Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway
  5. 5Department of Informatics, University of Oslo, Oslo, Norway
  6. 6Centre for Research-based Innovation Visual Intelligence, UiT The Arctic University of Norway,, Tromsø, Norway
  7. 7GSK Italy, Verona, Italy
  8. 8GSK Switzerland, Baar, Switzerland
  9. 9GSK Norway, Oslo, Norway
  10. 10Institute for Cancer Genetics and Informatics, Oslo University Hospital,, Oslo, Norway
  11. 11Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK

Abstract

Introduction/Background There is scarce real-world evidence on patients with advanced endometrial cancer (EC) treated with platinum-based chemotherapy in the literature. This study described the oncological outcome in groups by molecular classification.

Methodology This retrospective cohort study included patients referred to The Norwegian Radium Hospital, Oslo University Hospital (OUH), Norway who were diagnosed or operated for EC at OUH between January 2006 and December 2017. Patients with Stage III/IV EC treated with platinum-based chemotherapy after hysterectomy and with sufficient tumor tissue available at the biobank were molecularly classified as pathogenic polymerase epsilon (POLE)-mutated, mismatch repair deficient (MMRd), p53 abnormal, or no specific molecular profile (NSMP).

Results Of 264 patients, 263 were molecularly classified, 10 (4%) as POLE-mutated, 67 (26%) as MMRd, 117 (44%) as p53 abnormal and 69 (26%) as NSMP. One patient could not be molecularly characterized. Median age was 68 (61–74) years with a median follow up time of 5.3 (2.2–10.3) years. Patients with MMRd tumors had significantly longer time to recurrence (HR 0.43, 95% CI: 0.27–0.67, p=0.0001) and longer cancer-specific survival (HR 0.36, 95%CI: 0.22–0.58, p<0.0001) than patients with mismatch repair proficient (MMRp) tumors. Compared to patients with NSMP tumors, patients with p53 abnormal tumors had shorter cancer-specific survival (HR 1.78, 95% CI: 1.19–2.65) while patients with MMRd tumors had longer cancer-specific survival (HR 0.50, 95% CI: 0.29–0.87). Patients with POLE tumors had the longest cancer-specific survival (HR 0.32, 95% 0.08–1.32).

Conclusion Results show that molecular classification is prognostic in patients with advanced-stage endometrial cancer. Based on the recently reported clinical trials of a checkpoint inhibitor added to platinum-based chemotherapy in advanced and recurrent EC, patients with MMRd, and maybe also p53 abnormal tumors, have a better clinical outcome when treated with this combination treatment

Disclosures This supported collaborative study was funded by GSK (SCS: 219026)

KL: Receipt of grants/research supports: GSK, research funding paid to

Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisa

BM, DS: Stockholder: GSK, Other: Employee GSK

HE: Other: Employee GSK

GK: Stockholder: Novo Nordic

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