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 Baghdadi; Emily K. Hill; Premal H. Thaker; Veena S. John; Stephen Welch; Amanda N. Fader; Matthew A. Powell; Carol Aghajanian

doi:10.1056/NEJMoa2302312

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

^*Corresponding author for this work

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

206 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 language	English (US)
Pages (from-to)	2159-2170
Number of pages	12
Journal	New England Journal of Medicine
Volume	388
Issue number	23
DOIs	https://doi.org/10.1056/NEJMoa2302312
State	Published - 2023

Funding

Supported by grants (U10CA180868 and U10CA180822) from the National Cancer Institute (NCI). Funding was provided by Merck through a cooperative research and developmental agreement with the NCI. Merck also provided supplemental funding to NRG Oncology for this trial. Drs. Aghajanian and O’Cearbhaill are supported in part by a grant (P30CA008748) from the NCI.

Keywords

Gynecologic Oncology
Hematology/Oncology
Obstetrics/Gynecology
Treatments in Oncology

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1056/NEJMoa2302312

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Eskander, R. N., Sill, M. W., Beffa, L., Moore, R. G., Hope, J. M., Musa, F. B., Mannel, R., Shahin, M. S., Cantuaria, G. H., Girda, E., Mathews, C., Kavecansky, J., Leath, C. A., Gien, L. T., Hinchcliff, E. M., Lele, S. B., Landrum, L. M., Backes, F., O'Cearbhaill, R. E., ... Aghajanian, C. (2023). Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. New England Journal of Medicine, 388(23), 2159-2170. https://doi.org/10.1056/NEJMoa2302312

@article{657fca8ad33b48d4ba1261f4d53fae1c,

title = "Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer",

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.).",

keywords = "Gynecologic Oncology, Hematology/Oncology, Obstetrics/Gynecology, Treatments in Oncology",

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

note = "Publisher Copyright: {\textcopyright} 2023 Massachusetts Medical Society.",

year = "2023",

doi = "10.1056/NEJMoa2302312",

language = "English (US)",

volume = "388",

pages = "2159--2170",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "23",

}

Eskander, RN, Sill, MW, Beffa, L, Moore, RG, Hope, JM, Musa, FB, Mannel, R, Shahin, MS, Cantuaria, GH, Girda, E, Mathews, C, Kavecansky, J, Leath, CA, Gien, LT, Hinchcliff, EM, Lele, SB, Landrum, LM, Backes, F, O'Cearbhaill, RE, Al Baghdadi, T, Hill, EK, Thaker, PH, John, VS, Welch, S, Fader, AN, Powell, MA & Aghajanian, C 2023, 'Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer', New England Journal of Medicine, vol. 388, no. 23, pp. 2159-2170. https://doi.org/10.1056/NEJMoa2302312

TY - JOUR

T1 - Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer

AU - Eskander, Ramez N.

AU - Sill, Michael W.

AU - Beffa, Lindsey

AU - Moore, Richard G.

AU - Hope, Joanie M.

AU - Musa, Fernanda B.

AU - Mannel, Robert

AU - Shahin, Mark S.

AU - Cantuaria, Guilherme H.

AU - Girda, Eugenia

AU - Mathews, Cara

AU - Kavecansky, Juraj

AU - Leath, Charles A.

AU - Gien, Lilian T.

AU - Hinchcliff, Emily M.

AU - Lele, Shashikant B.

AU - Landrum, Lisa M.

AU - Backes, Floor

AU - O'Cearbhaill, Roisin E.

AU - Al Baghdadi, Tareq

AU - Hill, Emily K.

AU - Thaker, Premal H.

AU - John, Veena S.

AU - Welch, Stephen

AU - Fader, Amanda N.

AU - Powell, Matthew A.

AU - Aghajanian, Carol

PY - 2023

Y1 - 2023

N2 - 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.).

AB - 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.).

KW - Gynecologic Oncology

KW - Hematology/Oncology

KW - Obstetrics/Gynecology

KW - Treatments in Oncology

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U2 - 10.1056/NEJMoa2302312

DO - 10.1056/NEJMoa2302312

M3 - Article

C2 - 36972022

AN - SCOPUS:85152015601

SN - 0028-4793

VL - 388

SP - 2159

EP - 2170

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 23

ER -

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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