Immune Checkpoint Inhibitor, Nivolumab, Combined with Chemotherapy Improved the Survival of Unresectable Advanced and Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Experience

Abstract

Patients with advanced esophageal squamous cell carcinoma (SCC) have a poor prognosis when treated with standard chemotherapy. Programmed death ligand 1 (PD-L1) expression in esophageal cancer has been associated with poor survival and more advanced stage. Immune checkpoint inhibitors, such as PD-1 inhibitors, showed benefits in advanced esophageal cancer in clinical trials. We analyzed the prognosis of patients with unresectable esophageal SCC who received nivolumab with chemotherapy, dual immunotherapy (nivolumab and ipilimumab), or chemotherapy with or without radiotherapy. Patients who received nivolumab with chemotherapy had a better overall response rate (ORR) (72% vs. 66.67%, p = 0.038) and longer overall survival (OS) (median OS: 609 days vs. 392 days, p = 0.04) than those who received chemotherapy with or without radiotherapy. In patients receiving nivolumab with chemotherapy, the duration of the treatment response was similar regardless of the treatment line they received. According to clinical parameters, liver and distant lymph nodes metastasis showed a trend of negative and positive impacts, respectively, on treatment response in the whole cohort and in the immunotherapy-containing regimen cohort. Nivolumab add-on treatment showed less gastrointestinal and hematological adverse effects, compare with chemotherapy. Here, we showed that nivolumab combined with chemotherapy is a better choice for patients with unresectable esophageal SCC.

Keywords: esophageal SCC; immune checkpoint inhibitor; ipilimumab; nivolumab.

Figure 1

Survival in different treatment groups. (A) Overall survival (OS) in different groups. Group 1: patients received nivolumab + chemotherapy; Group 2: patients received nivolumab + ipilimumab; Group 3: patients received chemotherapy with PF as first-line therapy. (B) Progression-free survival (PFS). Group 1: patients received nivolumab + chemotherapy as first-line therapy; Group 2: patients received nivolumab + ipilimumab; Group 3: patients received chemotherapy with PF as first-line therapy.

Figure 2

Survival and treatment response in patient who received the immunotherapy-containing regimen. (A) Overall survival (OS) in patient who received immunotherapy-containing regimen. (B) Progression-free survival (PFS) in patients who received an immunotherapy regimen. The duration of the treatment response was the same regardless of whether patients received first-line, second-line or third-line nivolumab + chemotherapy. (C) Response rates in patients who received an immunotherapy regimen.