Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial.

Adult Aged Antibodies, Monoclonal, Humanized / administration & dosage Antineoplastic Agents, Immunological / administration & dosage Antineoplastic Combined Chemotherapy Protocols / administration & dosage B7-H1 Antigen / antagonists & inhibitors Cisplatin / administration & dosage Deoxycytidine / administration & dosage Female Humans Male Middle Aged Nasopharyngeal Carcinoma / drug therapy Neoplasm Recurrence, Local / drug therapy Progression-Free Survival Gemcitabine

Journal

Nature medicine

ISSN: 1546-170X

Titre abrégé: Nat Med

Pays: United States

ID NLM: 9502015

Informations de publication

Date de publication:
09 2021

Historique:

received: 04 05 2021

accepted: 21 06 2021

pubmed: 4 8 2021

medline: 9 10 2021

entrez: 3 8 2021

Statut: ppublish

Résumé

Gemcitabine-cisplatin (GP) chemotherapy is the standard first-line systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In this international, double-blind, phase 3 trial (ClinicalTrials.gov identifier: NCT03581786), 289 patients with RM-NPC and no previous chemotherapy for recurrent or metastatic disease were randomized (1/1) to receive either toripalimab, a monoclonal antibody against human programmed death-1 (PD-1), or placebo in combination with GP every 3 weeks for up to six cycles, followed by monotherapy with toripalimab or placebo. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent review committee according to RECIST v.1.1. At the prespecified interim PFS analysis, a significant improvement in PFS was detected in the toripalimab arm compared to the placebo arm: median PFS of 11.7 versus 8.0 months, hazard ratio (HR) = 0.52 (95% confidence interval (CI): 0.36-0.74), P = 0.0003. An improvement in PFS was observed across key subgroups, including PD-L1 expression. As of 18 February 2021, a 40% reduction in risk of death was observed in the toripalimab arm compared to the placebo arm (HR = 0.603 (95% CI: 0.364-0.997)). The incidence of grade ≥3 adverse events (AEs) (89.0 versus 89.5%), AEs leading to discontinuation of toripalimab/placebo (7.5 versus 4.9%) and fatal AEs (2.7 versus 2.8%) was similar between the two arms; however, immune-related AEs (39.7 versus 18.9%) and grade ≥3 infusion reactions (7.5 versus 0.7%) were more frequent in the toripalimab arm. In conclusion, the addition of toripalimab to GP chemotherapy as a first-line treatment for patients with RM-NPC provided superior PFS compared to GP alone, and with a manageable safety profile.

Identifiants

DOI: 10.1038/s41591-021-01444-0 PMID: 34341578

pubmed: 34341578

doi: 10.1038/s41591-021-01444-0

pii: 10.1038/s41591-021-01444-0

doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0

Antineoplastic Agents, Immunological 0

B7-H1 Antigen 0

CD274 protein, human 0

Deoxycytidine 0W860991D6

toripalimab 8JXN261VVA

Cisplatin Q20Q21Q62J

Gemcitabine 0

Banques de données

ClinicalTrials.gov

['NCT03581786']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1536-1543

Commentaires et corrections

Type : CommentIn

Type : ErratumIn

Informations de copyright

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