The FDA has granted approval to nivolumab (Opdivo®, Bristol Myers Squibb) for patients with completely resected esophageal or gastroesophageal junction (GEJ) cancer who have residual pathologic disease after prior neoadjuvant chemoradiotherapy.
"No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer," wrote the investigators of the phase 3 CheckMate 577 trial (NCT02743494), on which the approval was based, led by first author Ronan J. Kelly, MD, Director of Oncology for the Charles A. Sammons Cancer Center at Baylor University Medical Center in Dallas, Texas.
CheckMate 577 enrolled 794 patients with completely resected esophageal or GEJ cancer who had been previously treated with concurrent chemoradiotherapy and who had residual pathologic disease. Patients were randomized in a 2:1 ratio to receive nivolumab 240 mg or placebo every two weeks for 16 weeks, followed by nivolumab 480 mg or placebo every four weeks for up to one year. The primary end point was disease-free survival, defined as the time between randomization and first recurrence or death.
At a median follow-up of 24.4 months, patients receiving nivolumab experienced a statistically significant increase in median disease-free survival compared with placebo (22.4 vs 11.0 months, hazard ratio 0.69). The improvement in disease-free survival was seen regardless of tumor programmed death ligand 1 (PD-L1) expression status and histology.
Adverse events occurring in at least 20% of patients receiving nivolumab included 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. Grade 3 or 4 adverse events occurred in 13% of patients receiving nivolumab and in 6% of those receiving placebo, with treatment discontinuation occurring in 9% and 3% of patients, respectively.
"Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo," concluded Dr. Kelly and colleagues in their April 2021 publication of the trial's results in The New England Journal of Medicine.
The recommended dose of nivolumab as adjuvant therapy for resected esophageal or GEJ cancer is 240 mg every two weeks or 480 mg every four weeks, administered as 30-minute intravenous infusions, for a total treatment duration of one year.
For More Information
Clinicaltrials.gov (2021). An investigational immuno-therapy study of nivolumab or placebo in participants with resected esophageal or gastroesophageal junction cancer (CheckMate 577). NLM identifier: NCT02743494.
US Food & Drug Administration (2021). FDA approves nivolumab for resected esophageal or GEJ cancer. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-resected-esophageal-or-gej-cancer
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