Article Text
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