About NRG GY018: Pembrolizumab Plus Chemotherapy in Endometrial Cancer

John Nakayama, MD, gynecologic oncologist at Allegheny Health Network, discusses the significance of the NRG GY018 study (NCT03914612) in endometrial cancer.

The phase 3, randomized, placebo-controlled NRG-GY018 study evaluated pembrolizumab (Keytruda) in combination with carboplatin and paclitaxel for the treatment of patients with measurable stage III or IVA, stage IVB, or recurrent endometrial cancer. The primary end point of the study was progression-free survival. Secondary end points included incidence of adverse events (AEs), objective tumor response, duration of objective response, overall survival, quality-of-life, incidence of pembrolizumab treatment and self-reported neurotoxicity, concordance between institutional MMR immunohistochemistry (IHC) testing and centralized MMR IHC, effect of pembrolizumab on PFS and overall survival by PD-L1 IHC, and association between PD-L1 IHC and MMR status.

The combination demonstrated a statistically significant and clinically meaningful improvement in PFS among patients with stage III-IV or recurrent endometrial carcinoma regardless of mismatch repair (MMR) status.

With pembrolizumab plus chemotherapy in the MMR deficient (dMMR) population, the median progression-free survival (PFS) was not reached compared with 7.6 months in the placebo arm (HR, 0.30; 95% CI, 0.19-0.48; P <.00001). Among patients included in the MMR proficient (pMMR) population, the median PFS was 13.1 months with the combination of pembrolizumab and chemotherapy vs 8.7 months with the placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.00001).1

In the NRG-GY018 study, treatment was associated with AEs in a total of 15% of patients. The frequency of grade 3 or 4 Aes were similar in both MMR populations, and AEs of interest occurred more frequently with pembrolizumab.

Transcription:

0:09 | GY018 was reported recently. This is a trial that looked at patients with both recurrent and frontline endometrial cancer. It used the combination of carboplatin and paclitaxel along with pembrolizumab with pembrolizumab monotherapy as maintenance therapy. What it showed was that there was a significant progression-free survival in the patients that were treated on the pembrolizumab arm, and this was despite MMR or MSI status, while the patients that had an MMR deficiency had a longer improvement than those with a proficient status.

REFERENCE

Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170. doi:10.1056/NEJMoa2302312