Adding pembrolizumab to standard chemotherapy improves progression-free survival (PFS) for patients with advanced or recurrent endometrial cancer, according to research presented at the 2023 SGO Annual Meeting on Women’s Cancer.1
In this phase 3 trial, the addition of pembrolizumab improved PFS in patients with mismatch repair-deficient (dMMR) and mismatch repair-proficient (pMMR) disease.
“[W]e saw clinically meaningful improvement in PFS in both study populations — an encouraging new finding,” study presenter Ramez N. Eskander, MD, of the University of California San Diego, said in a statement.2
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Dr Eskander and colleagues conducted the phase 3 NRG-GY018 trial (ClinicalTrials.gov Identifier: NCT03914612) in patients with measurable stage III/IVA or measurable or nonmeasurable stage IVB or recurrent endometrial cancer.1 Patients could have received adjuvant chemotherapy, but they must have completed it at least 12 months prior to enrollment.
On study, all patients received carboplatin and paclitaxel every 3 weeks for 6 cycles. Patients were also randomly assigned to receive placebo or pembrolizumab (200 mg every 3 weeks) for 6 cycles. Patients then received maintenance placebo or pembrolizumab (400 mg) every 6 weeks for up to 14 additional cycles.
In the efficacy analyses, the dMMR cohort included 112 patients in the pembrolizumab arm and 113 patients in the placebo arm. The pMMR cohort included 293 patients in the pembrolizumab arm and 295 in the placebo arm.
In the dMMR cohort, the median PFS was not reached in the pembrolizumab arm and was 7.6 months in the placebo arm (hazard ratio [HR], 0.30; 95% CI, 0.19-0.48; P <.00001). The 12-month PFS rate was 74% in the pembrolizumab arm and 38% in the placebo arm.
In the pMMR cohort, the median PFS was 13.1 months in the pembrolizumab arm and 8.7 months in the placebo arm (HR, 0.54; 95% CI, 0.41-0.71; P <.00001).
“The addition of pembrolizumab to carboplatin and paclitaxel, followed by pembrolizumab maintenance, resulted in a 70% and 46% reduction in the risk of disease progression or death in the dMMR and pMMR patients, respectively,” Dr Eskander said during his presentation.
In the safety analyses, the dMMR cohort included 109 patients in the pembrolizumab arm and 106 patients in the placebo arm. The pMMR cohort included 276 patients in the pembrolizumab arm and 274 in the placebo arm.
In the dMMR cohort, grade 3-5 adverse events (AEs) occurred in 63.3% of patients in the pembrolizumab arm and 47.2% of patients in the placebo arm. In the pMMR cohort, grade 3-5 AEs occurred in 55.1% and 45.3% of patients, respectively.
Grade 5 AEs occurred in 3 patients from the dMMR cohort (1 in the pembrolizumab arm). The causes of death were cardiac arrest, sepsis, and lower gastrointestinal hemorrhage.
Grade 5 AEs occurred in 8 patients from the pMMR cohort (6 in the pembrolizumab arm). Causes of death were sepsis (n=4), cardiac arrest (n=2), small intestinal obstruction (n=1), and sudden death not otherwise specified (n=1).
This study was also published in The New England Journal of Medicine.3
Disclosures: This research was partly supported by Merck. Dr Eskander declared affiliations with AstraZeneca, Cardiff Oncology, Clovis Oncology, Daiichi Sankyo, Eisai, Ellevar Therapeutics, Gilead, GSK/Tesaro, ImmunoGen, Merck, Mersana, Myriad, Novocure, and Seagen.
References
1. Eskander RN, Sill MW, Beffa L, et al. NRG GY018/Keynote-868: A phase III randomized, placebo-controlled study of pembrolizumab in addition to paclitaxel and carboplatin for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer. SGO 2023. March 25-28, 2023.
2. Two clinical trials reveal addition of immunotherapy to chemotherapy regimen increases progression-free survival in endometrial cancer patients. Society of Gynecologic Oncology. News release. Published March 26, 2023.
3. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer.N Engl J Med. Published online March 27, 2023. doi:10.1056/NEJMoa2302312
