Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10395637" target="_blank" >RIV/00064203:_____/19:10395637 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/19:10395637 RIV/61989592:15110/19:73594296 RIV/00843989:_____/19:E0107801

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=G-nrw-BI_f" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=G-nrw-BI_f</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S0140-6736(18)32409-7" target="_blank" >10.1016/S0140-6736(18)32409-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Popis výsledku v původním jazyce

Background: First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods: This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (&gt;=18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (&gt;=50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator&apos;s choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0.0122, p=0.0120, and p=0.0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings: From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12.8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (&gt;=50% hazard ratio 0.69, 95% CI 0.56-0.85, p=0.0003; &gt;=20% 0.77, 0.64-0.92, p=0.0020, and &gt;=1% 0.81, 0.71-0.93, p=0.0018). The median surival values by TPS population were 20.0 months (95% CI 15.4-24.9) for pembrolizumab versus 12.2 months (10.4-14.2) for chemotherapy, 17.7 months (15.3-22.1) versus 13.0 months (11.6-15.3), and 16.7 months (13.9-19.7) versus 12.1 months (11.3-13.3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation: The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding: Merck Sharp &amp; Dohme. (C) 2019 Elsevier Ltd

Název v anglickém jazyce

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

Popis výsledku anglicky

Background: First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods: This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (&gt;=18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (&gt;=50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator&apos;s choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0.0122, p=0.0120, and p=0.0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings: From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12.8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (&gt;=50% hazard ratio 0.69, 95% CI 0.56-0.85, p=0.0003; &gt;=20% 0.77, 0.64-0.92, p=0.0020, and &gt;=1% 0.81, 0.71-0.93, p=0.0018). The median surival values by TPS population were 20.0 months (95% CI 15.4-24.9) for pembrolizumab versus 12.2 months (10.4-14.2) for chemotherapy, 17.7 months (15.3-22.1) versus 13.0 months (11.6-15.3), and 16.7 months (13.9-19.7) versus 12.1 months (11.3-13.3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation: The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding: Merck Sharp &amp; Dohme. (C) 2019 Elsevier Ltd

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30203 - Respiratory systems

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

The Lancet

ISSN

0140-6736

e-ISSN

—

Svazek periodika

393

Číslo periodika v rámci svazku

10183

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

1819-1830

Kód UT WoS článku

000466858700032

EID výsledku v databázi Scopus

2-s2.0-85064607320