Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer

Ramez N. Eskander, Michael W. Sill, Lindsey Beffa, Richard G. Moore, Joanie M. Hope, Fernanda B. Musa, Robert Mannel, Mark S. Shahin, Guilherme H. Cantuaria, Eugenia Girda, Cara Mathews, Juraj Kavecansky, Charles A. Leath, Lilian T. Gien, Emily M. Hinchcliff, Shashikant B. Lele, Lisa M. Landrum, Floor Backes, Roisin E. O'Cearbhaill, Tareq Al BaghdadiEmily K. Hill, Premal H. Thaker, Veena S. John, Stephen Welch, Amanda N. Fader, Matthew A. Powell, Carol Aghajanian

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

Background Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. Methods In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. Results In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. Conclusions In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).

Original languageEnglish
Pages (from-to)2159-2170
Number of pages12
JournalNew England Journal of Medicine
Volume388
Issue number23
DOIs
StatePublished - 2023

Keywords

  • Gynecologic Oncology
  • Gynecologic Oncology
  • Hematology/Oncology
  • Obstetrics/Gynecology
  • Treatments in Oncology

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