Benefit of pembrolizumab in dMMR, newly diagnosed, high-risk endometrial cancer

In patients with newly diagnosed, high-risk endometrial cancer who underwent surgery with curative intent and had no evidence of disease post-operatively, the addition of pembrolizumab to adjuvant chemotherapy, with or without radiotherapy, improved survival only in patients with deficient mismatch repair status (dMMR). This was the main result of the ENGOT-en11/GOG-3053/KEYNOTE-B21 study.

Patients with high-risk endometrial cancer are generally treated with systemic adjuvant chemotherapy with or without radiotherapy [1]. In the advanced, metastatic, or recurrent setting, adding pembrolizumab to chemotherapy significantly improves progression-free survival (PFS), regardless of mismatch repair status [2].

The randomised, double-blind, phase 3 ENGOT-en11/GOG-3053/KEYNOTE-B21 study (NCT04634877) evaluated the addition of pembrolizumab versus placebo to adjuvant chemotherapy, with or without radiotherapy, in patients with newly diagnosed, high-risk endometrial cancer who underwent surgery with curative intent and had no evidence of disease post-operatively. In both study arms, 25% of the participants had a dMMR status.

“In the total population [n=1,095], we did not observe a difference in disease-free survival (DFS) – one of the primary endpoints – between the pembrolizumab and placebo arm. The HR was 1.02 with a P-value of 0.57, so a negative result,” said Dr Toon van Gorp (UZ Leuven, Belgium) [3,4]. However, subgroup analysis showed a significant benefit of pembrolizumab in patients with dMMR status (n=281): HR 0.31 (95% CI 0.14–0.69). In this subgroup, DFS rate at 24 months was 92% versus 80% (see Figure). “We observed 3 recurrence events in the pembrolizumab arm versus 23 in the placebo arm.”

Figure: Disease-free survival with pembrolizumab plus chemotherapy in KEYNOTE-B21 [3]

1. Oaknin A, et al. Ann Oncol 2022;33:860-877.
2. Eskander RN, et al. N Eng J Med 2023;388:2159-2170.
3. Van Gorp T, et al. ENGOT-en11/GOG-3053/KEYNOTE-B21: A phase III study of pembrolizumab or placebo in combination with adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer. Abstract LBA28, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
4. Van Gorp T, et al. Ann Oncol 2024;Aug 23. DOI: 10.1016/j.annonc.2024.08.2242.

 

Copyright ©2024 Medicom Medical Publishers



Posted on 4 November 20245 November 2024