On June 10, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) for patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapy.
Efficacy was investigated in ATTRACTION-3, a multicenter, randomized, active-controlled, open-label trial in 419 patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma. Patients who were refractory or intolerant to at least one fluoropyrimidine- and platinum‑based regimen were randomly assigned to receive nivolumab at 240 mg by intravenous infusion over 30 minutes every 2 weeks (n = 210), or investigator’s choice of taxane chemotherapy consisting of docetaxel (75 mg/m2 intravenously every 3 weeks) or paclitaxel (100 mg/m2 intravenously once a week for 6 weeks followed by 1 week off) (n = 209).
The major efficacy outcome measure was overall survival. Additional efficacy outcome measures were overall response rate, response duration, and progression-free survival as assessed by the investigator using RECIST 1.1.
The trial demonstrated a statistically significant improvement in overall survival. Median overall survival for patients receiving nivolumab was 10.9 months (95% confidence interval [CI] = 9.2–13.3) compared with 8.4 months (95% CI = 7.2–9.9) for patients receiving investigator’s choice of taxane chemotherapy (hazard ratio [HR] = 0.77, 95% CI = 0.62–0.96, P = .0189). Overall survival benefit was observed regardless of tumor programmed cell death ligand 1 expression level. The overall response rate was 19.3% (95% CI = 13.7%–26%) in the nivolumab arm vs 21.5% (95% CI = 15.4%–28.8%) in the taxane chemotherapy arm, with a median duration of response of 6.9 months (95% CI = 5.4–11.1) and 3.9 months (95% CI = 2.8–4.2), respectively. The trial did not demonstrate an improvement in progression-free survival (HR = 1.1, 95% CI = 0.9–1.3).
The most common adverse reactions in ≥ 10% patients receiving nivolumab were rash, decreased appetite, diarrhea, constipation, musculoskeletal pain, upper respiratory tract infection, cough, pyrexia, pneumonia, anemia, fatigue, pruritus, nausea, and hypothyroidism.
The recommended nivolumab dose for patients with esophageal squamous cell carcinoma is 240 mg every 2 weeks or 480 mg every 4 weeks.