ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43927554" target="_blank" >RIV/00064173:_____/24:43927554 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10485492 RIV/00216208:11120/24:43927554 RIV/00064165:_____/24:10485492

Výsledek na webu

<a href="https://doi.org/10.1016/j.annonc.2024.08.2242" target="_blank" >https://doi.org/10.1016/j.annonc.2024.08.2242</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.annonc.2024.08.2242" target="_blank" >10.1016/j.annonc.2024.08.2242</a>

Jazyk výsledku

angličtina

Název v původním jazyce

ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

Popis výsledku v původním jazyce

BACKGROUND: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent pMMR and dMMR endometrial cancer (EC), with greater magnitude of benefit in the dMMR phenotype. We evaluated addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly-diagnosed, high-risk EC without any residual macroscopic disease following curative-intent surgery. METHODS: Patients with histologically confirmed high-risk (FIGO stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology) EC following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200mg or placebo Q3W for 6 cycles added to carboplatin-paclitaxel followed by pembrolizumab 400mg or placebo Q6W for 6 cycles per treatment assignment. Radiotherapy was at the investigator&apos;s discretion. Primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. RESULTS: 1095 patients were randomised (pembrolizumab, n=545; placebo, n=550). At this interim analysis (data cutoff, 4-March2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group (hazard ratio, 1.02 [95% CI, 0.79-1.32]; P=0.570). Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI, 0.14-0.69) in the dMMR population (n=281) and 1.20 (95% CI, 0.91-1.57) in the pMMR population (n=814). Grade &gt;=3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. CONCLUSION: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly-diagnosed, high-risk, all-comer EC. Preplanned subgroup analyses for stratification factors suggests pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable.

Název v anglickém jazyce

ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

Popis výsledku anglicky

BACKGROUND: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent pMMR and dMMR endometrial cancer (EC), with greater magnitude of benefit in the dMMR phenotype. We evaluated addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly-diagnosed, high-risk EC without any residual macroscopic disease following curative-intent surgery. METHODS: Patients with histologically confirmed high-risk (FIGO stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology) EC following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200mg or placebo Q3W for 6 cycles added to carboplatin-paclitaxel followed by pembrolizumab 400mg or placebo Q6W for 6 cycles per treatment assignment. Radiotherapy was at the investigator&apos;s discretion. Primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. RESULTS: 1095 patients were randomised (pembrolizumab, n=545; placebo, n=550). At this interim analysis (data cutoff, 4-March2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group (hazard ratio, 1.02 [95% CI, 0.79-1.32]; P=0.570). Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI, 0.14-0.69) in the dMMR population (n=281) and 1.20 (95% CI, 0.91-1.57) in the pMMR population (n=814). Grade &gt;=3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. CONCLUSION: Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly-diagnosed, high-risk, all-comer EC. Preplanned subgroup analyses for stratification factors suggests pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30214 - Obstetrics and gynaecology

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Annals of Oncology

ISSN

0923-7534

e-ISSN

1569-8041

Svazek periodika

35

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

968-980

Kód UT WoS článku

001353629400001

EID výsledku v databázi Scopus

2-s2.0-85205537265