Nivolumab plus chemotherapy in first-line metastatic non-small-cell lung cancer: results of the phase III CheckMate 227 Part 2 trial.

chemotherapy first line immunotherapy nivolumab nonsquamous non-small-cell lung cancer

Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
20 Nov 2023
Historique:
received: 17 05 2023
revised: 09 10 2023
accepted: 18 10 2023
medline: 22 11 2023
pubmed: 22 11 2023
entrez: 21 11 2023
Statut: aheadofprint

Résumé

In CheckMate 227 Part 1, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. We report results from CheckMate 227 Part 2, which evaluated nivolumab plus chemotherapy versus chemotherapy in patients with metastatic NSCLC regardless of tumor PD-L1 expression. Seven hundred and fifty-five patients with systemic therapy-naive, stage IV/recurrent NSCLC without EGFR mutations or ALK alterations were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus chemotherapy or chemotherapy. Primary endpoint was OS with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC. OS in all randomized patients was a hierarchically tested secondary endpoint. At 19.5 months' minimum follow-up, no significant improvement in OS was seen with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC [median OS 18.8 versus 15.6 months, hazard ratio (HR) 0.86, 95.62% confidence interval (CI) 0.69-1.08, P = 0.1859]. Descriptive analyses showed OS improvement with nivolumab plus chemotherapy versus chemotherapy in all randomized patients (median OS 18.3 versus 14.7 months, HR 0.81, 95.62% CI 0.67-0.97) and in an exploratory analysis in squamous NSCLC (median OS 18.3 versus 12.0 months, HR 0.69, 95% CI 0.50-0.97). A trend toward improved OS was seen with nivolumab plus chemotherapy versus chemotherapy, regardless of the tumor mutation status of STK11 or TP53, regardless of tumor mutational burden, and in patients with intermediate/poor Lung Immune Prognostic Index scores. Safety with nivolumab plus chemotherapy was consistent with previous reports of first-line settings. CheckMate 227 Part 2 did not meet the primary endpoint of OS with nivolumab plus chemotherapy versus chemotherapy in patients with metastatic nonsquamous NSCLC. Descriptive analyses showed prolonged OS with nivolumab plus chemotherapy in all-randomized and squamous NSCLC populations, suggesting that this combination may benefit patients with untreated metastatic NSCLC.

Sections du résumé

BACKGROUND BACKGROUND
In CheckMate 227 Part 1, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. We report results from CheckMate 227 Part 2, which evaluated nivolumab plus chemotherapy versus chemotherapy in patients with metastatic NSCLC regardless of tumor PD-L1 expression.
PATIENTS AND METHODS METHODS
Seven hundred and fifty-five patients with systemic therapy-naive, stage IV/recurrent NSCLC without EGFR mutations or ALK alterations were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus chemotherapy or chemotherapy. Primary endpoint was OS with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC. OS in all randomized patients was a hierarchically tested secondary endpoint.
RESULTS RESULTS
At 19.5 months' minimum follow-up, no significant improvement in OS was seen with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC [median OS 18.8 versus 15.6 months, hazard ratio (HR) 0.86, 95.62% confidence interval (CI) 0.69-1.08, P = 0.1859]. Descriptive analyses showed OS improvement with nivolumab plus chemotherapy versus chemotherapy in all randomized patients (median OS 18.3 versus 14.7 months, HR 0.81, 95.62% CI 0.67-0.97) and in an exploratory analysis in squamous NSCLC (median OS 18.3 versus 12.0 months, HR 0.69, 95% CI 0.50-0.97). A trend toward improved OS was seen with nivolumab plus chemotherapy versus chemotherapy, regardless of the tumor mutation status of STK11 or TP53, regardless of tumor mutational burden, and in patients with intermediate/poor Lung Immune Prognostic Index scores. Safety with nivolumab plus chemotherapy was consistent with previous reports of first-line settings.
CONCLUSIONS CONCLUSIONS
CheckMate 227 Part 2 did not meet the primary endpoint of OS with nivolumab plus chemotherapy versus chemotherapy in patients with metastatic nonsquamous NSCLC. Descriptive analyses showed prolonged OS with nivolumab plus chemotherapy in all-randomized and squamous NSCLC populations, suggesting that this combination may benefit patients with untreated metastatic NSCLC.

Identifiants

DOI: 10.1016/j.esmoop.2023.102065 PMID: 37988950
pubmed: 37988950
pii: S2059-7029(23)01306-6
doi: 10.1016/j.esmoop.2023.102065
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102065

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auteurs

H Borghaei (H)

Fox Chase Cancer Center, Philadelphia, USA. Electronic address: Hossein.Borghaei@fccc.edu.

K J O'Byrne (KJ)

Princess Alexandra Hospital and Queensland University of Technology, Brisbane, Australia.

L Paz-Ares (L)

Hospital Universitario 12 de Octubre, Universidad Complutense & CiberOnc, Madrid, Spain.

T-E Ciuleanu (TE)

Institutul Oncologic Prof. Dr. Ion Chiricuţă and UNF Iuliu Haţieganu University, Cluj-Napoca, Romania.

X Yu (X)

Zhejiang Cancer Hospital, Hangzhou, China.

A Pluzanski (A)

Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

A Nagrial (A)

Blacktown Hospital, Sydney, Australia.

L Havel (L)

Thomayer Hospital, Charles University, Prague, Czech Republic.

R D Kowalyszyn (RD)

Clínica Viedma, Viedma, Argentina.

C A Valette (CA)

Hôpital Sainte -Musse, Toulon, France.

J R Brahmer (JR)

Johns Hopkins, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, USA.

M Reck (M)

Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany.

S S Ramalingam (SS)

Winship Cancer Institute, Emory University, Atlanta, USA.

L Zhang (L)

Sun Yat-Sen University Cancer Center, Guangdong, China.

I Ntambwe (I)

Bristol Myers Squibb, Princeton, USA.

S K Rabindran (SK)

Bristol Myers Squibb, Princeton, USA.

F E Nathan (FE)

Bristol Myers Squibb, Princeton, USA.

D Balli (D)

Bristol Myers Squibb, Princeton, USA.

Y-L Wu (YL)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong, China.

Classifications MeSH