Can Pembrolizumab Improve dMMR Endometrial Cancer Outcomes?

TOPLINE:

Adding pembrolizumab to adjuvant chemotherapy in the first-line setting improved disease-free survival (DFS) in patients with high-risk endometrial cancer who have mismatch repair–deficient (dMMR) tumors, according to a subgroup analysis of a phase 3 study.

METHODOLOGY:

• About 25%-30% of patients with endometrial cancer harbor dMMR tumors, an inflamed phenotype that is associated with poor outcomes and has limited treatment options in the adjuvant setting.
• In the phase 3 ENGOT-en11/GOG-3053/KEYNOTE-B21 study, researchers found that adding pembrolizumab to adjuvant carboplatin-paclitaxel did not improve DFS in all patients with newly diagnosed, high-risk endometrial cancer following curative-intent surgery.
• In the current subgroup analysis, researchers assessed whether the 281 patients with dMMR tumors benefited from pembrolizumab. Patients were randomized to receive either pembrolizumab (n = 141) or placebo (n = 140) along with adjuvant chemotherapy with or without radiotherapy.
• The primary endpoint of this interim analysis was investigator-assessed DFS; the analysis also included blinded independent central review of DFS. The median follow-up duration was 24.6 months.

TAKEAWAY:

• Overall, DFS events occurred in eight patients (5.7%) in the pembrolizumab group — five deaths and three recurrences — while DFS events occurred in 25 patients (17.9%) in the placebo group — 2 deaths and 23 recurrences — as assessed by investigators.
• The 2-year DFS rates were 92.4% in the pembrolizumab group and 80.2% in the placebo group. Adding pembrolizumab to chemotherapy led to a significant improvement in DFS in this subgroup of patients with dMMR tumors (hazard ratio [HR], 0.31).
• However, the blinded independent central review of DFS identified more instances of recurrence in the pembrolizumab arm (9 with pembrolizumab vs 21 with placebo) compared with the investigator assessment (3 with pembrolizumab vs 23 with placebo), which suggest “substantial limitations” of blinded review in determining recurrence after surgery, the authors said.
• Adverse events of grade 3 or higher occurred in 78.6% of patients who received pembrolizumab vs 66.4% who received placebo. Adverse events led to deaths in three patients in the pembrolizumab arm and one in the control arm and discontinuation of any study drug in 33 patients (23.6%) in the pembrolizumab arm vs 19 patients (13.6%) in the control arm.

IN PRACTICE:

“Our data suggest a clinically relevant improvement in DFS when pembrolizumab is added to standard-of-care for the dMMR subgroup,” the authors wrote. “Longer-term follow-up of outcomes in the dMMR subgroup are planned” and will include overall survival.

SOURCE:

This study, led by Brian M. Slomovitz, MD, Mount Sinai Medical Center in Miami Beach, Florida, was published online in Journal of Clinical Oncology.

LIMITATIONS:

The study’s limitations included the lack of formal hypothesis testing and the relatively short follow-up period. Additionally, the findings may not be generalizable to all populations due to the specific inclusion criteria and the focus on high-risk endometrial cancer patients with dMMR tumors.

DISCLOSURES:

This study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. Two authors disclosed being employees of Merck Sharp & Dohme LLC, UK or USA, and owning stock and/or holding stock options in Merck & Co., Inc. Several authors declared having various ties with various sources. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.