On June 10, 2020, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo®) for patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

FDA Update

Efficacy was investigated in ATTRACTION-3 (NCT02569242), a multicenter, randomized (1:1), active-controlled, open-label trial in 419 patients with unresectable advanced, recurrent, or metastatic ESCC. Patients who were refractory or intolerant to at least one fluoropyrimidine- and platinum‑based regimen received nivolumab 240 mg by IV infusion over 30 minutes every two weeks (n = 210), or investigator’s choice of taxane chemotherapy consisting of docetaxel (75 mg/m2 via IV every three weeks) or paclitaxel (100 mg/m2 via IV once a week for six weeks followed by one week off) (n = 209). 

The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were overall response rate (ORR), response duration, and progression-free survival (PFS) as assessed by the investigator using RECIST 1.1.

The trial results demonstrated a statistically significant improvement in OS. Median OS for patients receiving nivolumab was 10.9 months (95% 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 (HR = 0.77; 95% CI = 0.62, 0.96; p = 0.0189). OS benefit was observed regardless of tumor PD-L1 expression level. The ORR was 19.3% (95% CI = 13.7, 26) in the nivolumab arm versus 21.5% (95% CI = 15.4, 28.8) in the taxane chemotherapy arm, with median response duration of 6.9 months (95% CI = 5.4, 11.1) and 3.9 months (95% CI = 2.8, 4.2), respectively. The trial results did not demonstrate an improvement in PFS (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 ESCC is 240 mg every two weeks or 480 mg every four weeks.

View full prescribing information for OPDIVO.

This review used Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. Nivolumab was granted priority review and orphan drug designation. A description of FDA’s expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient oncology investigational new drug applications, contact the Oncology Center of Excellence's Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.