Background
Phase III RCT included 419 patients with unresectable advanced or recurrent esophageal squamous cell carcinoma refractory or intolerant to one prior fluoropyrimidine- and platinum-based chemotherapy. Second-line setting.
Interventions and follow up
Arm A: Nivolumab 240 mg IV q2wk
Arm B: Investigator's choice taxane: paclitaxel 100 mg/m² D1,8,15,22,29,36 (q6wk) or docetaxel 75 mg/m² q3wk
Primary endpoint: OS
mFollow up: 10.5 vs 8.0 mo, arm A vs B
Arm B: Investigator's choice taxane: paclitaxel 100 mg/m² D1,8,15,22,29,36 (q6wk) or docetaxel 75 mg/m² q3wk
Primary endpoint: OS
mFollow up: 10.5 vs 8.0 mo, arm A vs B
Results
mOS: 10.9 vs 8.4 mo, arm A vs B (HR 0.77; 95% CI 0.62-0.96; P=.019)
12-mo OS: 47% vs 34%
ORR: 19% vs 22%
mPFS: 1.7 vs 3.4 mo
12-mo OS: 47% vs 34%
ORR: 19% vs 22%
mPFS: 1.7 vs 3.4 mo
Adverse events
Overall: Grade ≥3 treatment-related events 18% vs 63%, arm A vs B
Common nivolumab-related: rash, decreased appetite, diarrhea
Immune-related: hypothyroidism, pneumonitis/ILD (uncommon, generally manageable)
Common nivolumab-related: rash, decreased appetite, diarrhea
Immune-related: hypothyroidism, pneumonitis/ILD (uncommon, generally manageable)
Conclusions
Nivolumab significantly improved OS over taxane chemotherapy with a favorable safety profile in previously treated advanced esophageal squamous cell carcinoma, establishing a second-line option.
Key Limitations
OS benefit despite lower ORR and shorter PFS than chemotherapy, reflecting delayed immunotherapy effect. Predominantly Asian population may limit generalizability. Benefit observed irrespective of PD-L1.
Clinical Context
First-line chemoimmunotherapy (e.g., CheckMate 648) has largely supplanted second-line use, but ATTRACTION-3 supported nivolumab approval in pretreated esophageal SCC. ESMO recognizes immune checkpoint inhibition in advanced esophageal SCC.