Therese Sørlie

Real-world outcomes in molecular subgroups for patients with advanced or recurrent endometrial cancer treated with platinum-based chemotherapy.

There is scarce real-world evidence on patients with advanced/recurrent endometrial cancer treated with platinum-based chemotherapy. We assessed the oncological outcome in groups by molecular classification. This retrospective cohort study included patients with advanced/recurrent endometrial cancer treated with platinum-based chemotherapy after hysterectomy at The Norwegian Radium Hospital, Oslo University Hospital, Norway, between January 2006 and December 2017. Patients were molecularly classified as pathogenic POLE mutated, mismatch repair deficient, p53 abnormal, or no specific molecular profile. Time-to-recurrence and cancer-specific survival were calculated. We identified 264 advanced-stage patients (stage III/IV) and 96 patients with recurrent disease. The molecular classification was prognostic for time-to-recurrence (p < .0001) and cancer-specific survival (p < .0001) in patients with advanced disease, but the outcome did not differ significantly by molecular groups in recurrent patients. In all molecular groups, patients with stage III disease had longer time-to-recurrence and cancer-specific survival compared to patients with stage IV disease. The worst outcome was observed in patients with p53 abnormal tumors with an HR of 1.57 (95% CI 1.07 to 2.30) for time-to-recurrence and HR of 1.78 (95% CI 1.19 to 2.65) for cancer-specific survival in stage III/IV disease and an HR of 1.45 (95% CI 0.83 to 2.52) for time-to-recurrence and HR of 1.60 (95% CI 0.99 to 2.68) for cancer-specific survival in patients with recurrent disease. The few patients with POLE mutated tumors had favorable outcomes despite the advanced/recurrent disease status. Oncological outcomes differ by molecular groups, in particular among patients with advanced disease. Patients with p53 abnormal tumors have the worst outcome, while patients with POLE mutated tumors have favorable outcomes even with recurrent disease. Implementation of the addition of immunotherapy to chemotherapy is expected to lead to substantial improvement of outcome, particularly in patients with mismatch repair deficient advanced/recurrent disease. There is still a high unmet need in advanced/recurrent patients with p53 abnormal and no specific molecular profile tumors.