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CheckMate-648: Nivolumab with Ipilimumab or Chemotherapy Improves OS in Patients with Advanced Esophageal Squamous-Cell Carcinoma

2021 Year in Review - Gastrointestinal Cancer

Results from the CheckMate-648 study demonstrate that nivolumab added to either ipilimumab or chemotherapy improves overall survival in patients with advanced esophageal squamous-cell carcinoma.

The PD-1 pathway is involved in regulating host defenses that work to eliminate tumors and has been linked to cancer treatment outcomes along with overall survival (OS).1 Nivolumab, a PD-1 inhibitor, has been shown to improve survival rates when used to treat esophageal cancer.1 The phase 3 CheckMate-648 clinical trial is a global study evaluating the use of nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy alone as a first-line treatment for patients with advanced esophageal squamous-cell carcinoma (SCC). At the American Society of Clinical Oncology 2021 Annual Meeting, the initial results of OS and progression-free survival (PFS) from the CheckMate-648 study were presented.

The investigators recruited 970 adult patients with previously untreated unresectable advanced, recurrent, or metastatic esophageal SCC. Molecular testing was performed and 49% of participants were found to have tumors with PD-L1 ≥1%. The patients were randomized to 3 treatment groups. Nivolumab (240 mg every 2 weeks) plus a chemotherapy protocol consisting of fluorouracil and cisplatin every 4 weeks was given to one group. A second group received nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks). The third group received chemotherapy. The study’s primary end points were OS and PFS in patients with PD-L1–harboring tumors, whereas the secondary end points were OS and PFS in all patients. After ≥13 months of follow-up for all patients, a significant OS improvement was found in the patients who received nivolumab plus chemotherapy and nivolumab plus ipilimumab when compared with patients who received chemotherapy alone. A significant PFS improvement was discovered in participants with PD-L1 ≥1%-harboring tumors who received nivolumab and chemotherapy versus chemotherapy alone.

The objective response rate (ORR) in participants with tumors harboring PD-L1 ≥1% was 53% in the nivolumab and chemotherapy group; 35% in the nivolumab plus ipilimumab group; and 20% in the group that only received chemotherapy. The ORR in randomized patients was 47% in the nivolumab and chemotherapy group, 28% in the nivolumab plus ipilimumab group, and 27% in the group that only received chemotherapy.

Durable objective responses were seen in the groups treated with nivolumab when compared with the groups receiving chemotherapy alone. Safety data evaluation revealed an acceptable safety profile, with low incidence of treatment-related deaths across the 3 groups.

Source: Chau I, Doki Y, Ajani J, et al. Nivolumab (NIVO) plus ipilimumab (IPI) or NIVO plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): first results of the CheckMate 648 study. J Clin Oncol. 2021;39(suppl_18):LBA4001-LBA4001.


  1. Kato K, Doki Y, Ura T, et al. Long-term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer. Cancer Sci. 2020;111:1676-1684.
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