Pembrolizumab Combo Does Not Reach DFS End Point in Endometrial Cancer


Developers will work with investigators of the phase 3 KEYNOTE-B21 trial to share their findings with the scientific community.

Treatment with pembrolizumab produced a safety profile that was comparable with prior reports of the agent. Data highlighted no new safety signals.

Treatment with pembrolizumab produced a safety profile that was comparable with prior reports of the agent. Data highlighted no new safety signals.

Combining adjuvant pembrolizumab (Keytruda) with chemotherapy with or without radiotherapy did not reach the primary end point of disease-free survival (DFS) among patients with newly diagnosed, high-risk endometrial cancer who had previously treated withreceived surgery with curative intent, according to a press release on results from the phase 3 KEYNOTE-B21 trial (NCT04634877).1

In a prespecified interim analysis, an independent data monitoring committee reported that the pembrolizumab-based combination did not fulfill pre-specified statistical criteria for DFS vs placebo plus adjuvant chemotherapy with or without chemotherapyradiotherapy. Additionally, the committee did not formally assess the trial’s other primary end point of overall survival (OS) after the experimental regimen did not yield superior DFS.

Treatment with pembrolizumab produced a safety profile that was comparable with prior reports of the agent. Data highlighted no new safety signals.

Investigators are currently conducting a full assessment of the data and will collaborate with developers to share their findings with the scientific community.

“While these results were not what we had hoped, we are focused on continuing to build on the established role of [pembrolizumab] in advanced endometrial carcinoma through our approved indications, while rapidly progressing clinical research evaluating [pembrolizumab]-based combinations and other investigational candidates, including antibody-drug conjugates, in endometrial and other types of gynecologic malignancies,” Gursel Aktan, MD, PhD, vice president, global clinical development at Merck Research Laboratories, said in the press release.1

In the double-blind KEYNOTE-B21/ENGOT-en11/GOG-3053 trial, approximately 1095 patients were assigned to receive pembrolizumab at 200 mg every 3 weeks for 6 cycles or matched placebo in combination with standard chemotherapy for 4 or 6 cycles followed by pembrolizumab at 400 mg every 6 weeks for 6 more cycles or placebo. Patients were also eligible to receive radiotherapy.

The trial’s primary end points were DFS per investigator assessment or histopathologic confirmation of suspected disease recurrence and OS.2 Secondary end points included adverse effects and changes in health-related quality of life based on different European Organization for Research and Treatment of Cancer Quality of Life Questionnaires.

Patients 18 years and older with histologically confirmed endometrial carcinoma or carcinosarcoma and prior surgery with hysterectomy and bilateral salpingo-oophorectomy given with curative intent were eligible for enrollment on the trial. Additional eligibility criteria included having no prior radiation or systemic therapy, an ECOG performance status of 0 or 1 within a week of study entry, an available tumor tissue sample, and adequate organ function.

Those with recurrent endometrial carcinoma or carcinosarcoma or a uterine mesenchymal tumor were ineligible for enrollment. Patients were also unsuitable for study entry if they had stage IVB disease of any histology, residual tumor following surgery, an active autoimmune disease requiring management with systemic treatment within 2 years prior to entry, and a history of pneumonitis that needed to be managed with steroids. Having an active infection requiring systemic therapy was also grounds for exclusion from the trial.

The FDA previously approved pembrolizumab plus lenvatinib (Lenvima) for patients with advanced endometrial carcinoma that is notwho do not have mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) disease in July 2021.3 Supporting data for this approval came from the phase 3 KEYNOTE-755/Study 309 trial (NCT03517449), in which pembrolizumab/lenvatinib elicited statistically significant OS and progression-free survival improvements compared with investigator’s choice of chemotherapy.

The FDA also approved pembrolizumab monotherapy in dMMR or MSI-H advanced endometrial carcinoma in March 2022.4 The approval was based on results from the phase 2 KEYNOTE-158 trial (NCT02628067).


  1. Merck provides update on phase 3 KEYNOTE-B21 trial evaluating KEYTRUDA® (pembrolizumab) plus chemotherapy, with or without radiotherapy, for patients with newly diagnosed, high-risk endometrial cancer after surgery with curative intent. News release. Merck. May 9, 2024. Accessed May 9, 2024.
  2. Study of pembrolizumab (MK-3475) in combination with adjuvant chemotherapy with or without radiotherapy in participants with newly diagnosed endometrial cancer after surgery with curative intent (MK-3475-B21 /​ KEYNOTE-B21 /​ ENGOT-en11 /​ GOG-3053). Accessed May 9, 2024.
  3. FDA approves Keytruda (pembrolizumab) plus Lenvima (lenvatinib) combination for patients with certain types of advanced endometrial carcinoma. News release. Merck. July 22, 2021. Accessed May 9, 2024.
  4. FDA Approves pembrolizumab for advanced endometrial carcinoma. News Release. FDA. March 21, 2022. Accessed March 21, 2022.
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