Abstract
Overall survival and progression-free survival by PD-L1 status among endometrial cancer patients treated with pembrolizumab plus carboplatin/paclitaxel as compared to carboplatin/paclitaxel plus placebo in the NRG GY018 trial
Gynecologic oncology, Vol.190(Supplement 1), pp.S5-S5
11/2024
DOI: 10.1016/j.ygyno.2024.07.015
Abstract
Objectives
NRG GY018 identified a 70 % and 46 % reduction in the risk of disease progression or death in advanced-stage or recurrent MMR deficient (dMMR) and MMR proficient (pMMR) endometrial cancer (EC) patients treated with pembrolizumab plus carboplatin/paclitaxel (CP). The impact of PD-L1 expression levels on clinical outcomes among pMMR and dMMR EC patients is not well understood.
Methods
A total of 819 patients were randomized 1:1 to pembrolizumab + CP or placebo (PBO) + CP Q3W for 6 cycles, followed by maintenance pembrolizumab or PBO Q6W for up to 2 years. PD-L1 status was assessed by central laboratory evaluation utilizing 22C3 PharmDx immunohistochemistry (IHC) assay. A combined positive score (CPS), which is the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100, was calculated for each sample. The effect of PD-L1 expression levels (CPS <1 vs CPS ≥1) was examined in dMMR and pMMR patients treated with pembrolizumab or placebo. Analysis for overall survival (OS) was also conducted at the time of Interim Analysis 1 (IA1) for both the dMMR and pMMR EC patient populations.
Results
Overall survival analysis was immature at IA1 for both the dMMR and pMMR EC patient populations (pMMR information fraction 27.2 % [99 out of 364 events needed at final analysis]; dMMR information fraction 18.0 % [27 out of the 150 events needed at final analysis]). Treatment with pembrolizumab plus chemotherapy showed a directionally favorable improvement in OS compared with PBO plus chemotherapy in both the dMMR and pMMR EC cohorts: pMMR HR of 0.79 (95 % CI: 0.53–1.17; 1-sided nominal P = 0.1157), reflecting a 21 % reduction in the risk of death; dMMR HR of 0.55 (95 % CI: 0.25–1.19; 1-sided nominal P = 0.0617), representing a 45 % reduction in risk of death. The median OS in the pMMR cohort was similar for the pembrolizumab and PBO groups (27.96 months; 95 % CI: 21.42–NR in the pembrolizumab group, 27.37 months; 95 % CI: 19.52–NR in the PBO group). Median OS was not reached in either dMMR EC cohort. Importantly, when examining both PFS and OS by PD-L1 expression status (CPS <1 vs CPS ≥1), there was a significant improvement in PFS with pembrolizumab irrespective of PD-L1 expression level. In the PD-L1-positive pMMR EC cohort, the median PFS was 13.1 months with pembrolizumab versus 8.5 months with PBO (HR: 0.59; 95 % CI: 0.43–0.80). In the PD-L1-negative pMMR EC cohort, the median PFS was 15.1 months with pembrolizumab versus 11 months with PBO (HR: 0.44; 95 % CI: 0.26–0.75). The PFS HR favored pembrolizumab in the dMMR population irrespective of PD-L1 status (PD-L1-negative HR: 0.3 [95 % CI: 0.11–0.83]; PD-L1-positive HR: 0.27 [95 % CI: 0.16–0.47]).
Conclusions
Immature OS analysis (IA1) suggested a directionally favorable benefit with the addition of pembrolizumab to CP in both the dMMR and pMMR EC cohorts despite (%***pending) crossover to immunotherapy at progression. Incorporation of pembrolizumab resulted in a significant improvement in PFS irrespective of PD-L1 expression levels.
Details
- Title: Subtitle
- Overall survival and progression-free survival by PD-L1 status among endometrial cancer patients treated with pembrolizumab plus carboplatin/paclitaxel as compared to carboplatin/paclitaxel plus placebo in the NRG GY018 trial
- Creators
- Ramez Eskander - University of California San DiegoMichael Sill - Roswell Park Comprehensive Cancer CenterLindsey Beffa - Cleveland ClinicRichard Moore - University of Rochester Medical CenterJoanie Hope - Pacific Cancer Research Consortium NCORP, United StatesFernanda Musa - Pacific Cancer Research Consortium NCORP, United StatesRobert Mannel - University of Oklahoma Health Sciences CenterMark Shahin - Thomas Jefferson UniversityGuilherme Cantuaria - Georgia NCI Community Oncology Research, Atlanta, GA, United StatesEugenia Girda - Rutgers Cancer InstituteCara Mathews - Women & Infants Hospital of Rhode IslandJuraj Kavecansky - Kaiser PermanenteCharles Leath - University of Alabama at BirminghamLilian Gien - Sunnybrook Health Science CentreEmily Hinchcliff - Northwestern UniversityShashikant Lele - Roswell Park Comprehensive Cancer CenterLisa Landrum - Indiana University IndianapolisFloor Backes - The Ohio State UniversityRoisin O'Cearbhaill - Memorial Sloan Kettering Cancer CenterRebecca Liu - Michigan Cancer Research ConsortiumEmily Hill - University of Iowa, Iowa City, IA, United StatesPremal H. Thaker - Washington University in St. LouisVeena John - Northwell HealthMatthew Powell - Washington University in St. LouisCarol Aghajanian - Memorial Sloan Kettering Cancer Center
- Resource Type
- Abstract
- Publication Details
- Gynecologic oncology, Vol.190(Supplement 1), pp.S5-S5
- DOI
- 10.1016/j.ygyno.2024.07.015
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/2024
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984732542002771
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