On May 27, 2022, nivolumab was approved for use in combination with fluoropyrimidine- and platinum-based chemotherapy and in combination with ipilimumab for the first-line treatment of advanced or metastatic esophageal squamous cell carcinoma.1
Supporting Efficacy Data
Approval was based on findings from the open-label CheckMate 648 trial (ClinicalTrials.gov identifier NCT03143153). In the trial, 970 patients were randomly assigned to receive nivolumab at 240 mg on days 1 and 15, fluorouracil at 800 mg/m2/d on days 1 through 5, and cisplatin at 80 mg/m2 on day 1 in 4-week cycles (n = 321); nivolumab at 3 mg/kg every 2 weeks in combination with ipilimumab at 1 mg/kg every 6 weeks (n = 325); or fluorouracil and cisplatin given as previously mentioned (n = 324).
In the total population, median overall survival was 13.2 months (95% confidence interval [CI] = 11.1–15.7 months) in the nivolumab/chemotherapy group (hazard ratio [HR] = 0.74, 95% CI = 0.61–0.90, P = .0021, vs chemotherapy), 12.8 months (95% CI = 11.3–15.5 months) in the nivolumab/ipilimumab group (HR = 0.78, 95% CI = 0.65–0.95, P = .0110, vs chemotherapy), and 10.7 months (95% CI = 9.4–11.9 months) in the chemotherapy group.
Among 158, 158, and 157 patients with tumor cell PD-L1 expression ≥ 1%, median overall survival was 15.4 months with nivolumab/chemotherapy (HR = 0.54, P < .0001, vs chemotherapy), 13.7 months with nivolumab/ipilimumab (HR = 0.64, P = .0010, vs chemotherapy), and 9.1 months with chemotherapy.
How It Is Used
The recommended dose of nivolumab is 240 mg every 2 weeks or 480 mg every 4 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy or 3 mg/kg every 2 weeks or 360 mg every 3 weeks with ipilimumab at 1 mg/kg every 6 weeks.
In the CheckMate 648 trial, the most common adverse events of any grade with nivolumab/chemotherapy were nausea (65%), decreased appetite (51%), fatigue (47%), constipation (44%), and stomatitis (44%). The most common adverse events with nivolumab/ipilimumab were rash (31%), fatigue (28%), pyrexia (23%), nausea (22%), and diarrhea (22%).
Serious adverse events occurred in 62% of those given nivolumab/chemotherapy, most commonly pneumonia (11%) and dysphagia (7%), and in 69% of those given nivolumab/ipilimumab, most commonly pneumonia (10%), pyrexia (4.3%), and pneumonitis (4%). Adverse events led to discontinuation of treatment in 39% and
23% of the two groups, respectively. Fatal adverse events occurred in five patients (1.6%) in each group; they included pneumonitis, pneumatosis intestinalis, pneumonia, and acute kidney injury in the nivolumab/chemotherapy group and pneumonitis, interstitial lung disease, pulmonary embolism, and acute respiratory distress syndrome in the nivolumab/ipilimumab group.
Nivolumab has warnings/precautions for immune-mediated adverse reactions (which can occur in any organ system or tissue), infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving nivolumab.
1. Opdivo (nivolumab) injection, for intravenous use, prescribing information, Bristol-Myers Squibb Company, May 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125554s106lbl.pdf. Accessed June 6, 2022.