Dr Eskander on Pembrolizumab Plus Chemo in Advanced/Recurrent Endometrial Cancer

Ramez N. Eskander, MD, gynecologic oncologist, assistant professor, Obstetrics, Gynecology, and Reproductive Sciences, Moores Cancer Center, University of California, San Diego Health, discusses findings presented at the SGO 2024 annual meeting regarding key prespecified secondary end points from the phase 3 NRG GY018 trial (NCT03914612), which evaluated the addition of the pembrolizumab (Keytruda) to chemotherapy in patients with stage III/IVA or recurrent endometrial cancer.

The presentation included data on overall survival (OS), progression-free survival (PFS) based on PD-L1 expression status measured by the combined positive score (CPS), and both investigator-assessed and blinded independent central review (BICR) of PFS.

Findings showed that at data cutoff, OS data were immature at a median follow-up of 8.8 months (range, 0.1-37.0) in the pembrolizumab plus chemotherapy arm for the mismatch repair–proficient (pMMR) population (n = 294) and 8.4 months (range, 0.1-37.2) in the chemotherapy plus placebo arm (n = 294). However, a trend favoring the pembrolizumab combination was observed (HR, 0.79; 95% CI, 0.53-1.17; P = .1157). Patients in the experimental arm experienced a median OS of 27.96 months (95% CI, 21.42–not reached [NR]) compared with 27.37 (95% CI, 19.52-NR) in the placebo arm. Notably, 45.0% of patients in the control arm who discontinued study treatment received a subsequent PD-1/PD-L1 inhibitor compared with 19.3% of patients in the pembrolizumab arm.

Additionally, a favorable OS trend was observed with pembrolizumab plus chemotherapy in patients with mismatch repair–deficient (dMMR) disease (n = 110) vs chemotherapy plus placebo (n = 110; HR, 0.55; 95% CI, 0.25-1.19; P = .0617).

Furthermore, a PFS benefit for the pembrolizumab regimen was observed in patients with pMMR disease who had a PD-L1 CPS of at least 1 (HR, 0.59; 95% CI, 0.43-0.80) and those who had a PD-L1 CPS of less than 1 (HR, 0.44; 95% CI, 0.26-0.75). In the dMMR population, PFS benefits were also seen in those with a PD-L1 CPS of at least 1 (HR, 0.27; 95% CI, 0.16-0.47) and in patients with a PD-L1 CPS of less than 1 (HR, 0.30; 95% CI, 0.11-0.83).

Notably, BICR- and investigator-assessed PFS generated similar benefit signals for the pembrolizumab combination in the pMMR population (BICR, HR, 0.64; 95% CI, 0.49-0.85; P = .0008; investigator, HR, 0.57; 95% CI, 0.44-0.74; P < .0001) and in the dMMR population (BICR, HR, 0.45; 95% CI, 0.27-0.73; P = .0005; investigator, HR, 0.34; 95% CI, 0.22-0.53; P < .0001).