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Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial.
- Source :
-
Nature medicine [Nat Med] 2021 Sep; Vol. 27 (9), pp. 1536-1543. Date of Electronic Publication: 2021 Aug 02. - Publication Year :
- 2021
-
Abstract
- 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.<br /> (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Subjects :
- Adult
Aged
Antibodies, Monoclonal, Humanized adverse effects
Antineoplastic Agents, Immunological administration & dosage
Antineoplastic Combined Chemotherapy Protocols adverse effects
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen genetics
Cisplatin administration & dosage
Cisplatin adverse effects
Deoxycytidine administration & dosage
Deoxycytidine adverse effects
Deoxycytidine analogs & derivatives
Female
Humans
Male
Middle Aged
Nasopharyngeal Carcinoma immunology
Nasopharyngeal Carcinoma pathology
Neoplasm Recurrence, Local immunology
Neoplasm Recurrence, Local pathology
Progression-Free Survival
Gemcitabine
Antibodies, Monoclonal, Humanized administration & dosage
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Nasopharyngeal Carcinoma drug therapy
Neoplasm Recurrence, Local drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1546-170X
- Volume :
- 27
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 34341578
- Full Text :
- https://doi.org/10.1038/s41591-021-01444-0