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Nivolumab Combination Therapy in Advanced Esophageal Squamous Cell Carcinoma
Immune checkpoint inhibitors targeting tumor-cell PD-L1 have been approved to combine with first-line chemotherapy in advanced esophagogastric cancer and esophageal squamous cell cancer. Alternative checkpoint inhibitors are also yielding positive results in first-line trials. Investigators now report results from CheckMate 648, an open-label, industry-sponsored, phase 3 trial of first-line immune checkpoint inhibitor therapy in advanced squamous cell carcinoma of the esophagus. A total of 970 patients received one of three regimens: a 4-week cycle of chemotherapy alone (intravenous fluorouracil/cisplatin), chemotherapy plus nivolumab, or nivolumab plus ipilimumab. Patients' median age was 64, 70% were treated in Asia, half had PD-L1 expression ≥1%, and half had two or more sites of metastatic disease.
At a minimum follow-up of 13 months, overall survival was superior for nivolumab plus chemotherapy compared to chemotherapy alone in patients with PD-L1 expression ≥1% (15.4 vs. 9.1 months; hazard ratio, 0.54; P<0.001) and in all treated patients (13.2 vs. 10.7 months; HR, 0.74; P=0.002). However, there was no survival benefit in patients with PD-L1 expression >1%. Overall survival was also superior for nivolumab/ipilimumab compared with chemotherapy in patients with PD-L1 expression ≥1% (13.7 vs. 9.1 months; HR, 0.64; P=0.001) and in all treated patients (12.7 vs. 10.7 months; HR, 0.78; P=0.01). Again, there was no survival benefit in patients with TPS score <1% or CPS score <1%. Progression-free survival was superior for nivolumab plus chemotherapy compared with chemotherapy only in patients with TPS score >1% (6.9 vs. 4.4 months, HR 0.65, P =0.002). Response rates were higher for nivolumab plus chemotherapy than chemotherapy alone in patients with PD-L1 expression ≥1% (53% vs. 20%) and in all patients (47% vs. 27%), as was response duration (8.2 vs. 5.7 months and 8.2 months vs. 7.1 months). Improved response was seen for nivolumab/ipilimumab versus chemotherapy only in patients with PD-L1 expression ≥1% (rate, 35% vs 20%; duration, 11.8 vs 5.7 months). No new safety signals were observed.
This landmark trial in squamous cell cancer of the esophagus indicates a survival benefit over chemotherapy alone for nivolumab added to first-line chemotherapy and for the combination of nivolumab and ipilimumab. The benefit, not clearly stated by the authors but evident from review of data in the supplement, is limited to patients with PD-L1 expression ≥1%. Nivolumab added to chemotherapy or with ipilimumab will likely gain regulatory approval for this indication.
Doki Y et al.
Title: Nivolumab combination therapy in advanced esophageal squamous-cell carcinoma.
Source: N Engl J Med 2022 Feb 3; [e-pub]. (Abstract/FREE Full Text)