Keynote B-21: Pembrolizumab vs. Placebo in High-risk Endometrial Cancer

Keynote B-21

ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer - PubMed

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

PubMedT Van Gorp

Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy For Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors - PubMed

Mismatch repair-deficient (dMMR) endometrial cancer is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase 3 ENGOT-en11/GOG-3053/K …

PubMedBrian M Slomovitz

Trial in Clinical Context - Watch the Video

Keynote B21 - Pembrolizumab in High-Risk Endometrial Cancer (Video Explainer)

Video Explaining B-21 Trial

GYOEDU PlusShitanshu Uppal

Study Summaries (Combined)

Hypothesis:
Pembrolizumab combined with adjuvant chemotherapy (with or without radiotherapy) improves disease-free survival (DFS) and overall survival (OS) compared to chemotherapy and placebo in patients with newly diagnosed, high-risk endometrial cancer.

Inclusion Criteria:

• HIGH-RISK DISEASE with Post-surgery, no macroscopic residual disease
  • FIGO stage I/II of non-endometrioid histology
  • Endometrioid histology with p53/TP53 abnormality
  • Stage III/IVA of any histology
• ECOG 0 or 1.

Exclusion Criteria:

• Recurrent endometrial cancer or other specific tumor types like mesenchymal or neuroendocrine tumors.
• Known POLE mutation.
• Active autoimmune disease or systemic immunosuppression.

Primary End Point:
Disease-free survival (DFS) and overall survival (OS) in the intention-to-treat population.

Experimental Arm(s):

• Pembrolizumab (200 mg every 3 weeks for 6 cycles) + Carboplatin (AUC 5 or 6 mg/mL/min) + Paclitaxel (175 mg/m² every 3 weeks for 6 cycles)
• Option for external beam radiation therapy (EBRT) or brachytherapy following chemotherapy.
• Pembrolizumab maintenance: 400 mg every 6 weeks for 6 cycles.

Control Arm (Standard Therapy):

• Placebo + Carboplatin (AUC 5 or 6 mg/mL/min) + Paclitaxel (175 mg/m² every 3 weeks for 6 cycles).
• Optional radiotherapy as per the experimental arm.
• Placebo maintenance every 6 weeks for 6 cycles.

Results:

Radiation Therapy Proportions:

Experimental Arm (Pembrolizumab + Chemotherapy):

• External Beam Radiation Therapy (EBRT) with Cisplatin: 17.0%
• EBRT without Cisplatin: 57.4%
• Brachytherapy Only: 6.4%
• No Radiation Therapy (Neither EBRT nor Brachytherapy): 19.1%

Control Arm (Placebo + Chemotherapy):

• External Beam Radiation Therapy (EBRT) with Cisplatin: 18.6%
• EBRT without Cisplatin: 46.4%
• Brachytherapy Only: 6.4%
• No Radiation Therapy (Neither EBRT nor Brachytherapy): 28.6%

Full Analysis

• No significant improvement in DFS for the all-comer population.
• Pembrolizumab showed significant benefit in the dMMR subgroup but not in the pMMR subgroup.

Subset Analysis (dMMR)

• DFS events occurred in 8 patients (5.7%) in the pembrolizumab group versus 25 patients (17.9%) in the placebo group.
• No new safety signals were observed in this subgroup analysis.

Conclusions:
Adjuvant pembrolizumab did not improve DFS in the overall high-risk endometrial cancer population, but it showed meaningful DFS improvement in patients with dMMR tumors.

Limitations:

• No mature overall survival data at the interim analysis.
• Differences in radiation therapy usage across regions.
• The study did not meet its primary DFS endpoint for the general population.