Pembrolizumab plus chemo ups survival in advanced endometrial cancer across MMR subgroups

Adding pembrolizumab to standard chemotherapy resulted in a favourable overall survival (OS) benefit in patients with advanced or recurrent endometrial cancer compared with chemotherapy alone, regardless of mismatch repair (MMR) status, according to a key prespecified secondary analysis of the NRG-GY018 trial presented at the SGO 2024.

Among patients with mismatch repair-deficient (dMMR) disease, the median OS was not reached in both pembrolizumab and placebo treatment arms (hazard ratio [HR], 0.55; p=0.0617), translating to a 45-percent reduction in the risk of death.

Among patients with mismatch repair-proficient (pMMR) disease, the median OS was 27.96 months in patients treated with pembrolizumab plus chemo vs 27.37 months in those who received placebo plus chemo (HR, 0.79; p=0.1157), which translated to a 21-percent reduction in the risk of death.

“Despite the high number of patients in the control arm receiving subsequent immunotherapy (55 percent [dMMR cohort] 45 percent [pMMR cohort]), the addition of pembrolizumab to chemo [with carboplatin and paclitaxel] and continued as maintenance resulted in a numeric and directionally favourable improvement in median OS,” said lead author Dr Ramez Eskander from Moores Cancer Center at the University of California San Diego Health, San Diego, California, US.

This NRG-GY018 phase III trial evaluated 810 patients with measurable stage III/IVA or measurable/nonmeasurable stage IVB or recurrent endometrial cancer who were stratified according to MMR status (dMMR cohort: n=222 and pMMR cohort: n=588). Participants were randomized to receive chemo* with either pembrolizumab 200 mg IV or placebo every 3 weeks for six cycles, followed by pembrolizumab or placebo maintenance every 6 weeks for up to 14 cycles.

Majority of the patients had a PD-L1 CPS** ≥1, with 71–87 percent of dMMR and pMMR patients in both treatment arms.

Improved PFS regardless of PD-L1 status

In the dMMR population, the median progression-free survival (PFS) was improved in the pembrolizumab arm than in the placebo arm regardless of PD-L1 CPS status (not reached vs 8.3 months; HR, 0.27 [PD-L1 CPS ≥1] and 12.0 vs 4.9 months; HR, 0.30 [PD-L1 CPS <1]).

Similar PFS benefits were seen in the pMMR population, in which the addition of pembrolizumab to chemo led to longer median PFS than treatment with placebo plus chemo, both among patients with PD-L1 CPS ≥1 (13.1 vs 8.5 months; HR, 0.59) or <1 (15.1 vs 11.0 months; HR, 0.44).

Eskander noted that in this cohort of patients enrolled on NRG-GY018, the vast majority had PD-L1 CPS score ≥1 and that the therapeutic benefit of pembrolizumab persisted irrespective of PD-L1 status.

PFS by investigator, BICR assessments

In the dMMR cohort, both investigator- and BICR-assessed PFS were not reached in the pembrolizumab arm and were 8.3 and 14.1 months, respectively, in the placebo arm (HRs, 0.34; p<0.0001 and 0.45; p=0.0005).

In the pMMR cohort, median PFS per investigator was 13.1 months in the pembrolizumab arm vs 8.7 months in the placebo arm (HR, 0.57; p< 0.0001). Median PFS by BICR*** was 19.5 vs 11.0 months (HR, 0.64; p=0.0008).

“Taken together, the PFS benefit, as per investigator and BICR, was consistent and highly concordant … in showing meaningful improvement in outcome with the incorporation of pembrolizumab therapy,” said Eskander.

“Overall, these data strongly support the incorporation of pembrolizumab in conjunction with chemotherapy and continued as maintenance for the treatment and management of patients with advanced or recurrent endometrial cancer, irrespective of the MMR status,” he concluded.