K Kato, J Ajani, Y Doki, J Xu, L Wyrwicz, S Motoyama, T Ogata, H Kawakami, C-H Hsu, A Adenis, F El Hajbi, M Di Bartolomeo, M Ignez Braghiroli, E Holtved, T Makino, M Blum Murphy, J Zhang, P Sharma, B He, M Lei, Y Matsumura, Y Kitagawa, I Chau
Nivolumab-containing treatment regimens continued to demonstrate clinically meaningful OS benefit versus chemotherapy at the 5-year follow-up, with no new safety signals. These data further support nivolumab in combination with chemotherapy or ipilimumab as first-line treatment for patients with advanced ESCC.
BACKGROUND: Nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit compared with chemotherapy for patients with previously untreated advanced esophageal squamous cell carcinoma (ESCC). We report OS and additional analyses at a minimum follow-up of 5 years.
PATIENTS AND METHODS: The open-label, phase III CheckMate 648 trial (NCT03143153) enrolled patients with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC. Patients were randomized 1:1:1 to nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy. The primary endpoints were OS and progression-free survival (PFS) by blinded independent central review (BICR) in patients with tumor cell programmed death ligand 1 (PD-L1) expression ≥1%. Key secondary endpoints included OS and PFS by BICR in all randomized patients.
RESULTS: In total, 970 patients were randomized. At the 5-year minimum follow-up, OS improvement continued to be observed with nivolumab plus chemotherapy versus chemotherapy (HR 0.62, 95% CI 0.48-0.79) and nivolumab plus ipilimumab versus chemotherapy (HR 0.62, 95% CI 0.48-0.80) in patients with tumor cell PD-L1 ≥1%. OS benefit was also observed in all randomized patients (HR 0.77, 95% CI 0.65-0.92 for both nivolumab plus chemotherapy and nivolumab plus ipilimumab versus chemotherapy). PFS benefit was observed with nivolumab plus chemotherapy versus chemotherapy in the tumor cell PD-L1 ≥1% (HR 0.67, 95% CI 0.51-0.88) population, but not with nivolumab plus ipilimumab versus chemotherapy (HR 1.03, 95% CI 0.78-1.35). Among all treated patients, grade 3/4 treatment-related adverse events were observed in 49% of patients in the nivolumab plus chemotherapy group, 33% in the nivolumab plus ipilimumab group, and 37% in the chemotherapy group.
CONCLUSIONS: Nivolumab-containing treatment regimens continued to demonstrate clinically meaningful OS benefit versus chemotherapy at the 5-year follow-up, with no new safety signals. These data further support nivolumab in combination with chemotherapy or ipilimumab as first-line treatment for patients with advanced ESCC.