TY - JOUR
T1 - First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer
T2 - A Randomized, Open-Label, Phase III Trial
AU - The ENGOT-en9/LEAP-001 Investigators
AU - Marth, Christian
AU - Moore, Richard G.
AU - Bidziński, Mariusz
AU - Pignata, Sandro
AU - Ayhan, Ali
AU - Rubio, M. Jesús
AU - Beiner, Mario
AU - Hall, Marcia
AU - Vulsteke, Christof
AU - Braicu, Elena Ioana
AU - Sonoda, Kenzo
AU - Wu, Xiaohua
AU - Frentzas, Sophia
AU - Mattar, André
AU - Lheureux, Stephanie
AU - Chen, Xiaojun
AU - Hasegawa, Kosei
AU - Magallanes-Maciel, Manuel
AU - Choi, Chel Hun
AU - Shalkova, Mariia
AU - Kaen, Diego
AU - Wang, Peng Hui
AU - Berger, Regina
AU - Okpara, Chinyere E.
AU - McKenzie, Jodi
AU - Yao, Lili
AU - Orlowski, Robert
AU - Khemka, Vivek
AU - Gilbert, Lucy
AU - Makker, Vicky
AU - Kaen, Diego Lucas
AU - Gomez Abuin, Gonzalo
AU - Zamora, Liliana Beatriz
AU - Alfie, Margarita Sonia
AU - Casarini, Ignacio Alfredo
AU - Harrison, Michelle
AU - Ananda, Sumitra
AU - Shannon, Catherine Margaret
AU - Friedlander, Michael
AU - Meniawy, Tarek
AU - Gao, Bo
AU - Baron-Hay, Sally
AU - Diakos, Connie
AU - Polterauer, Stephan
AU - Petru, Edgar
AU - De Bock, Marlies
AU - Baurain, Jean Francois
AU - Van Gorp, Toon
AU - Altintas, Sevilay
AU - An, Ruifang
N1 - Publisher Copyright:
© 2025 American Society of Clinical Oncology.
PY - 2025/3/20
Y1 - 2025/3/20
N2 - PURPOSELenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101) that evaluated len + pembro versus chemotherapy in first-line aEC.METHODSPatients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m2 plus carboplatin AUC 6 mg/mL/min once every 3 weeks. Primary end points were PFS and OS, evaluated in the mismatch repair-proficient (pMMR) and all-comers populations. Noninferiority was assessed for OS at final analysis (FA) for len + pembro versus chemotherapy (multiplicity-adjusted, one-sided nominal alpha,.0159; null hypothesis-tested hazard ratio [HR], 1.1).RESULTSEight hundred forty-two patients were randomly assigned (len + pembro, n = 420 [pMMR population, n = 320]; chemotherapy, n = 422 [pMMR population, n = 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len + pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4) months (HR, 0.91 [95% CI, 0.76 to 1.09]; descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len + pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]; noninferiority P =.246, not statistically significant per multiplicity control strategy) and among all-comers was 37.7 (32.2 to 43.6) versus 32.1 (27.2 to 35.7) months (HR, 0.93 [95% CI, 0.77 to 1.12]). Grade ≥3 treatment-related adverse events occurred in 331/420 (79%) versus 274/411 (67%) treated patients.CONCLUSIONFirst-line len + pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.
AB - PURPOSELenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) in the phase III Study 309/KEYNOTE-775. We report results from the phase III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101) that evaluated len + pembro versus chemotherapy in first-line aEC.METHODSPatients with stage III to IV or recurrent, radiographically apparent EC and no previous chemotherapy or disease progression ≥6 months after neo/adjuvant platinum-based chemotherapy were randomly assigned 1:1 to lenvatinib 20 mg once daily plus pembrolizumab 200 mg once every 3 weeks or paclitaxel 175 mg/m2 plus carboplatin AUC 6 mg/mL/min once every 3 weeks. Primary end points were PFS and OS, evaluated in the mismatch repair-proficient (pMMR) and all-comers populations. Noninferiority was assessed for OS at final analysis (FA) for len + pembro versus chemotherapy (multiplicity-adjusted, one-sided nominal alpha,.0159; null hypothesis-tested hazard ratio [HR], 1.1).RESULTSEight hundred forty-two patients were randomly assigned (len + pembro, n = 420 [pMMR population, n = 320]; chemotherapy, n = 422 [pMMR population, n = 322]). At FA (data cutoff, October 2, 2023), median PFS (95% CI) in the pMMR population was 9.6 (8.2 to 11.9) versus 10.2 (8.4 to 10.5) months with len + pembro versus chemotherapy (hazard ratio [HR], 0.99 [95% CI, 0.82 to 1.21]) and among all-comers was 12.5 (10.3 to 15.1) versus 10.2 (8.4 to 10.4) months (HR, 0.91 [95% CI, 0.76 to 1.09]; descriptive analyses). Median OS (95% CI) in the pMMR population was 30.9 (25.4 to 37.7) versus 29.4 (26.2 to 35.4) months with len + pembro versus chemotherapy (HR, 1.02 [95% CI, 0.83 to 1.26]; noninferiority P =.246, not statistically significant per multiplicity control strategy) and among all-comers was 37.7 (32.2 to 43.6) versus 32.1 (27.2 to 35.7) months (HR, 0.93 [95% CI, 0.77 to 1.12]). Grade ≥3 treatment-related adverse events occurred in 331/420 (79%) versus 274/411 (67%) treated patients.CONCLUSIONFirst-line len + pembro did not meet prespecified statistical criteria for PFS or OS versus chemotherapy in pMMR aEC.
UR - https://www.scopus.com/pages/publications/105000878312
U2 - 10.1200/JCO-24-01326
DO - 10.1200/JCO-24-01326
M3 - 文章
C2 - 39591551
AN - SCOPUS:105000878312
SN - 0732-183X
VL - 43
SP - 1083
EP - 1100
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -
SDG 3 Good Health and Well-being