FDA Approves Nivolumab for Resected Esophageal or GEJ Cancer

Efficacy was evaluated in a randomized, multicenter, double-blind trial (CHECKMATE-577; NCT02743494) of 794 patients with completely resected (negative margins) esophageal or GEJ cancers who had residual pathologic disease following concurrent chemoradiotherapy. Patients were randomized 2:1 to receive either nivolumab 240 mg or placebo every two weeks for 16 weeks followed by 480 mg of nivolumab or placebo every four weeks beginning at week 17 for up to one year of treatment.

The main efficacy outcome measure was disease-free survival (DFS), defined as the time between randomization date and the first recurrence (local, regional, or distant from the primary resected site) date or death from any cause, as assessed by the investigator prior to subsequent anticancer therapy.

The findings demonstrated a statistically significant improvement in DFS for patients receiving nivolumab compared to those in the placebo arm. Median DFS was 22.4 months (95% CI = 16.6, 34.0) versus 11 months (95% CI = 8.3, 14.3), respectively (hazard ratio = 0.69; 95% CI = 0.56, 0.85; p = 0.0003). DFS benefit was observed regardless of tumor PD-L1 expression and histology.

The most common adverse reactions (≥ 20%) were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, and vomiting.

The recommended nivolumab dose for adjuvant treatment of resected esophageal or GEJ cancer is 240 mg every two weeks or 480 mg every four weeks for a total treatment duration of one year. Both doses are administered by IV infusion over 30 minutes.

View the full prescribing information for nivolumab (https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125554s092lbl.pdf).

The review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies. 

The review used the Real Time Oncology Review (https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program) pilot program, which streamlined data submission prior to the entire clinical application, and Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission to facilitate FDA’s assessment.

Nivolumab received orphan drug designation for the indication. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics). 

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.  

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov)