92% Disease-Free Survival With Postsurgical Pembrolizumab in dMMR Endometrial Cancer

Endometrial cancer, the most common type of uterine cancer, is one of the most frequent cancers in women, with approximately 420 thousand women diagnosed worldwide each year.

This cancer follows a more complex course in patients with mismatch repair-deficient (dMMR) tumors. Found in approximately 25-30% of cases, this tumor type is characterized by:

• An increased mutational burden,
• A high density of tumor-infiltrating lymphocytes (TILs),
• High PD-L1 expression, and
• Other immunological markers that lead the disease to become more resistant to conventional treatments such as chemotherapy.

Standard treatment approaches are often inadequate in this patient group, and the risk of recurrence is high.

• Related topic: Durvalumab Plus Chemotherapy: FDA Approval for First-Line Treatment of dMMR Endometrial Cancer

The ENGOT-en11 / GOG-3053 / KEYNOTE-B21 Trial

On 16 October 2024, Journal of Clinical Oncologypublished the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 trial, which investigated the efficacy of adding pembrolizumab to standard postsurgical adjuvant chemotherapy in patients with early-stage endometrial cancer and dMMR tumors, and reported important findings.

This article discusses the study methods, results, and their implications for clinical practice.

Study Methods

Newly diagnosed patients with high-risk endometrial cancer who were eligible for adjuvant treatment after surgery were assigned to two main groups.

• Treatment Protocol:

  • One group received 200 mg of pembrolizumab every 6 weeks alongside chemotherapy, while the other received chemotherapy plus placebo. Both groups received standard adjuvant chemotherapy consisting of carboplatin and paclitaxel.

  • After this six-week treatment, 400 mg of pembrolizumab or placebo continued to be administered every six weeks for one year.

  • Radiotherapy was left to the clinical circumstances of the patient and the investigator’s discretion.

• Assessment Criteria:

  • Disease-free survival (DFS) was designated as one of the primary study endpoints.

  • All patients were followed using radiological examinations and histopathological confirmation.

  • Adverse effects and patient-reported outcomes (PROs) were recorded in detail during treatment.

Results

Initial study analyses showed a striking improvement in disease-free survival rates among patients with dMMR tumors receiving pembrolizumab:

• Disease-Free Survival (DFS):

  • The two-year disease-free survival rate in the pembrolizumab group was 92.4% (95% CI, 84.4-96.4%).

  • In the placebo group, this rate was 80.2% (95% CI, 70.8-86.9%).

  • The hazard ratio (HR) was 0.31 (95% CI, 0.14-0.69), indicating that pembrolizumab significantly reduced the risk of disease progression.

Adverse Effects:

• • Adverse effects in the pembrolizumab group were generally manageable, and no treatment-related deaths were reported during the study.

  • Immune-related adverse effects, in particular, were closely monitored and kept under control.

Commentary

This study demonstrates the applicability of pembrolizumab as adjuvant treatment for patients with endometrial cancer and dMMR tumors.

• Biological Advantages:

  • The immunological sensitivity of dMMR tumors, arising from an increased neoantigen burden and extensive interaction with the immune system, enables a better response to immunotherapies such as pembrolizumab.

• Clinical Applications:

  • This treatment strategy offers promise to patients at high risk of recurrence by significantly improving disease-free survival rates.

  • Long-term follow-up data will allow a better understanding of its effects on overall survival.

In conclusion,using pembrolizumab as adjuvant treatment offers a new treatment paradigm for patients with endometrial cancer and dMMR tumors. If translated into clinical practice, these findings could reduce recurrence rates and substantially improve patients’ quality of life. Future studies should evaluate the effects of this strategy in a broader patient population.