Pembrolizumab Plus Chemotherapy Did Not Improve Disease-Free Survival in Patients With High-Risk Endometrial Cancer
In a phase 3, randomized, double-blind, placebo-controlled, parallel-group trial, researchers found that pembrolizumab plus chemotherapy did not improve disease-free survival (DFS) in newly diagnosed, high-risk patients with endometrial cancer. However, subgroup analyses showed that the pembrolizumab plus chemotherapy combination improved DFS in patients with mismatch repair-deficient (dMMR) tumors.
Although previous studies have found that the first-line treatment option of pembrolizumab plus chemotherapy offers a clinical benefit for patients with advanced, metastatic, or recurrent mismatch repair proficient (pMMR) and dMMR endometrial cancers, researchers set out to determine whether pembrolizumab plus adjuvant chemotherapy would improve DFS among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery.
Researchers included 1095 patients with histologically confirmed high-risk endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, as well as no prior history of radiotherapy or systemic therapy.
Patients were randomly assigned (1:1) to receive adjuvant pembrolizumab 200 mg or placebo every 3 weeks for six cycles plus carboplatin-paclitaxel, followed by pembrolizumab 400 mg or placebo every 6 weeks for four or six cycles (pembrolizumab, n = 545 patients; placebo, n = 550 patients. The primary endpoints were DFS and overall survival in the intention-to-treat population. The median follow-up was 23.9 months.
At the interim analysis, 119 (22%) DFS events occurred in the pembrolizumab group, and 121 (22%) occurred in the placebo group (hazard ratio = 1.02 [95% CI, 0.79 to 1.32]; P = .570). Kaplan-Meier estimates of 2-year DFS rates were 75% and in the pembrolizumab and 76% in the placebo groups.
In prespecified analyses, the HRs for DFS favored the pembrolizumab group in the dMMR subgroup (n = 281; HR = 0.31 [95% CI, 0.14 to 0.69] compared with no benefit for DFS in the pMMR subgroup (n = 814; HR = 1.20 [95% CI, 0.91 to 1.57]).
Looking at safety, adverse events of grade 3 or 4 occurred in 386 of 543 patients (71%) in the pembrolizumab group and 348 of 549 patients (63%) in the placebo group. Additionally, no treatment-related grade 5 adverse events were observed.
“Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer,” the researchers concluded. “Preplanned subgroup analyses for stratification factors suggests pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumors. Safety was manageable.”
Reference
Van Gorp T, Cibula D, Lv W, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase 3 study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Ann Oncol. Published online August 23, 2024. doi:10.1016/j.annonc.2024.08.2242