On 3rd February 2023, MSD announced that its clinical trial evaluating the combination of pembrolizumab and chemotherapy in the treatment of patients with advanced or recurrent endometrial carcinoma met its primary endpoint by significantly prolonging the progression-free survival (PFS). This news gives hope to patients suffering from this disease, who until now had limited treatment options and a poor prognosis.
Endometrial carcinoma is the most common gynaecological cancer in Europe, with a 5-year prevalence of 34.7% (445,805 cases).1 Patients with advanced-stage or recurrent endometrial cancer face a poor prognosis with limited treatment options. KEYTRUDA® (pembrolizumab) is an anti-programmed death receptor-1 (PD-1) monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes and increasing the ability of the immune system to help fight tumour cells. The phase 3 NRG-GY018 trial evaluated the efficacy and safety of combining pembrolizumab plus chemotherapy to treat patients with stage III-IV or recurrent endometrial carcinoma, compared to chemotherapy.2
The phase 3 NRG-GY018 trial enrolled 819 patients with stage III, IVA, IVB or recurrent endometrial cancer who have undergone mismatch repair (MMR) testing. In order to be eligible for the study, patients could not have received prior chemotherapy for the treatment of endometrial cancer. However, prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemo-radiotherapy) was allowed provided that this adjuvant chemotherapy was completed at least 12 months prior to the study. Patients were randomised to pembrolizumab plus chemotherapy (paclitaxel and carboplatin) or placebo plus chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints include overall survival, objective response rate, duration of response and safety. Approximately 70% of patients were proficient (p)MMR, and 30% deficient (d)MMR.2
In this study, pembrolizumab plus chemotherapy resulted in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in both the dMMR and pMMR study populations. The safety profile of pembrulizumab was consistent with that observed in previously reported studies, and no new safety signals were identified.2
Although the complete results of this trial are awaited, this news is encouraging and shows the potential of pembrolizumab plus chemotherapy to effectively treat patients with stage III to IV or recurrent disease, regardless of mismatch repair status.2