Nivolumab plus chemotherapy or ipilimumab versus chemotherapy in patients with advanced esophageal squamous cell carcinoma (CheckMate 648): 29-month follow-up from a randomized, open-label, phase III trial.
Date
2024-05-01ICR Author
Author
Kato, K
Doki, Y
Chau, I
Xu, J
Wyrwicz, L
Motoyama, S
Ogata, T
Kawakami, H
Hsu, C-H
Adenis, A
El Hajbi, F
Di Bartolomeo, M
Braghiroli, MI
Holtved, E
Makino, T
Blum Murphy, M
Amaya-Chanaga, C
Patel, A
Hu, N
Matsumura, Y
Kitagawa, Y
Ajani, J
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data. METHODS: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. Primary endpoints were OS and progression-free survival (PFS) by blinded independent central review. Hierarchical testing was performed first in patients with tumor cell programmed death ligand 1 (PD-L1) expression of ≥1% and then in the overall population. RESULTS: A total of 970 patients were randomly assigned. After 29 months of minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in OS versus chemotherapy (hazard ratio [HR] = 0.59 [95% CI: 0.46-0.76]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.78 [95% CI: 0.65-0.93]) and with nivolumab plus ipilimumab versus chemotherapy (HR = 0.62 [95% CI: 0.48-0.80]) in patients with tumor cell PD-L1 expression of ≥1% and in the overall population (HR = 0.77 [95% CI: 0.65-0.92]). In patients with tumor cell PD-L1 expression of ≥1%, nivolumab plus chemotherapy demonstrated PFS benefit versus chemotherapy (HR = 0.67 [95% CI: 0.51-0.89]); PFS benefit was not observed with nivolumab plus ipilimumab versus chemotherapy (HR = 1.04 [95% CI: 0.79-1.36]). Among all treated patients (n = 936), Grade 3-4 treatment-related adverse events were reported in 151 (49%, nivolumab plus chemotherapy), 105 (32%, nivolumab plus ipilimumab), and 110 (36%, chemotherapy) patients. CONCLUSIONS: Nivolumab plus chemotherapy and nivolumab plus ipilimumab continued to demonstrate clinically meaningful OS benefit versus chemotherapy with no new safety signals identified with longer follow-up, further supporting use as first-line standard treatment options for patients with advanced ESCC.
Collections
Subject
cancer management
check point control
chemotherapy
clinical cancer research
clinical trials
esophageal squamous cell carcinoma
Humans
Ipilimumab
Nivolumab
Male
Esophageal Squamous Cell Carcinoma
Antineoplastic Combined Chemotherapy Protocols
Female
Esophageal Neoplasms
Middle Aged
Aged
Follow-Up Studies
Adult
Progression-Free Survival
B7-H1 Antigen
Aged, 80 and over
Language
eng
Date accepted
2024-04-21
License start date
2024-05-01
Citation
Cancer Medicine, 2024, 13 (9), pp. e7235 -
Publisher
WILEY