Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial.

Historically, the treatment of patients with advanced stage or recurrent endometrial cancer included paclitaxel plus carboplatin. Immunotherapy in combination with chemotherapy resulted in improved clinical outcomes in several solid tumors. In the phase 3 NRG GY018 study, pembrolizumab plus chemotherapy significantly improved investigator-assessed progression-free survival (PFS; primary endpoint) versus placebo plus chemotherapy in patients with advanced/metastatic/recurrent endometrial cancer regardless of mismatch repair status. Here we report on key secondary endpoints and exploratory analyses. Patients were women ≥18 years old with newly diagnosed stage III or IVA endometrial cancer with measurable disease, or stage IVB or recurrent endometrial cancer with or without measurable disease. Patients (n = 810) were randomized (1:1) to pembrolizumab or placebo plus paclitaxel-carboplatin followed by maintenance pembrolizumab or placebo for up to 24 months. Overall survival was a secondary endpoint and PFS per RECIST v.1.1 by blinded independent central review was an exploratory endpoint. Overall survival data were immature; hazard ratios favored pembrolizumab (mismatch repair-proficient: 0.79 (0.53-1.17); 1-sided nominal P = 0.1157; mismatch repair-deficient: 0.55 (0.25-1.19); 1-sided nominal P = 0.0617). Hazard ratios (95% confidence intervals) for PFS per blinded independent central review favored pembrolizumab (mismatch repair-proficient: 0.64 (0.49-0.85); P = 0.0008; mismatch repair-deficient: 0.45 (0.27-0.73); P = 0.0005). These findings further support the use of pembrolizumab plus chemotherapy as first-line treatment for patients with advanced stage or recurrent endometrial cancer regardless of mismatch repair status. ClinicalTrials.gov identifier: NCT03914612 .