Pembrolizumab Plus Chemotherapy For Patients With High-Risk Endometrial Cancer

According to results from the phase 3 ENGOT-en11/GOG-3053/KEYNOTE-B21 study, adjuvant pembrolizumab plus chemotherapy did not improve the disease-free survival (DFS) among patients with newly diagnosed, high-risk endometrial cancer.

Toon Van Gorp, MD, Leuven Cancer Institute, Leuven, Belgium, and coauthors explained that pembrolizumab plus chemotherapy has provided clinically meaningful benefit in the first-line setting for patients with advanced, metastatic, or recurrent endometrial cancer. While a benefit was seen for both patients with mismatch repair-deficient (dMMR) and -proficient (pMMR) disease, there was a “greater magnitude of benefit in the dMMR phenotype.”

There were 1095 patients with newly diagnosed high-risk endometrial cancer without any residual disease following curative-intent surgery who had not received prior radiotherapy or systemic therapy included in this study. Patients were randomized on a 1-to-1 basis to receive 200 mg pembrolizumab (n = 545) or placebo (n = 550) every 3 weeks for 6 cycles plus carboplatin-paclitaxel, followed by either 400 mg pembrolizumab or placebo every 6 weeks for 6 cycles per treatment assignment. Investigators determined whether patients also underwent radiotherapy. The primary end points for this study were investigator-assessed DFS and overall survival (OS) in the intention-to-treat population.

The interim analysis had a data cut-off date of March 4, 2024. The estimated 2-year DFS rate was 75% in the pembrolizumab arm and 76% in the placebo arm (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.79 to 1.32; P = .570). The HR for DFS was 0.31 among patients with dMMR disease (n = 281), and 1.20 among patients with pMMR disease (n = 814). 

Additionally, protocol-prespecified subgroup analyses of patients with dMMR tumors were conducted. There were 141 patients with dMMR disease in the pembrolizumab group and 140 in the placebo group. Among those patients, DFS events occurred in 8 patients in the pembrolizumab group and 25 patients in the placebo group. The estimated 2-year DFS rates were 92.4% in the pembrolizumab group and 80.2% in the placebo group. 

In the intention-to-treat population, grade ≥3 adverse events occurred in 71% of patients in the pembrolizumab arm and 63% of patients in the placebo arm. There were no treatment-related grade 5 adverse events.

In the report of the protocol-prespecified subgroup analyses, Brian Slomovitz, MD, Mount Sinai Medical Center, Miami Beach, Florida, and coauthors wrote, “No difference in DFS was seen between the treatment groups in the [intention-to-treat] population.” They went on, “However, in this protocol-prespecified non-analytical subgroups analysis, the addition of pembrolizumab to adjuvant carboplatin-paclitaxel (±radiotherapy) suggested improvement for DFS that was clinically relevant, especially considering the study population was at high-risk for recurrence.” 

Source:

Van Gorp T, Cibula D, Lv W, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: A randomised, double-blind, phase III, study of pembrolizumab or placebo plus adjuvant chemotherapy with or withour radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Ann Oncol. 2024;35(11):968-980. doi:10.1016/j.annonc.2024.08.2242

Slomovitz B, Cibula D, Lv W, et al. Pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy for newly diagnosed, high-risk endometrial cancer: Results in mismatch repair-deficient tumors. J Clin Oncol. Published online: October 16, 2024. doi:10.1200/JCO-24-01887