Nivolumab Injection


On October 9, 2015, the U. S. Food and Drug Administration approved nivolumab (Opdivo Injection, Bristol-Myers Squibb Company), for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Opdivo. This approval expands the indication for nivolumab in NSCLC with progression on or after platinum-based chemotherapy to include non-squamous histologies. FDA approved nivolumab for patients with metastatic squamous NSCLC with progression on or after platinum-based chemotherapy on March 4, 2015.  
Approval was based on demonstration of an improvement in overall survival (OS) in an international, multi-center, open-label, randomized trial comparing nivolumab to docetaxel in patients with metastatic non-squamous NSCLC with progression on or after platinum-based chemotherapy. 
The clinical trial enrolled 582 patients who were randomized (1:1) to receive nivolumab 3 mg/kg every 2 weeks (n=292) or docetaxel 75 mg/m2 every 3 weeks (n=290) until disease progression or unacceptable toxicity. The trial excluded patients with autoimmune disease, medical conditions requiring systemic immunosuppression, symptomatic interstitial lung disease, or untreated brain metastasis.   
The trial demonstrated improvement in OS with a hazard ratio of 0.73 (95% CI: 0.60, 0.89); p <0.002. The median OS was 12.2 months in patients treated with nivolumab and 9.4 months in patients treated with docetaxel. The trial also demonstrated a significant improvement in overall response rate (19% vs 12%) in the nivolumab and docetaxel arms, respectively; the median response duration was 17 months in the nivolumab arm and 6 months in the docetaxel arm. There was no significant difference in progression-free survival. 
Archival tumor specimens were evaluated for tumor PD-L1 expression (PD-L1 immunohistochemistry 28-8 pharmDx assay) following completion of the trial in 78% of the study population. Across this subgroup, 46% were PD-L1 negative (less than 1% of tumor cells expressing PD-L1) and 54% of patients had greater than or equal to 1% of tumor cells expressing PD-L1. Pre-specified subgroup analyses suggested that patients with PD-L1 positive NSCLC (PD-L1 expression in greater than or equal to 1% of tumor cells) had a larger survival treatment effect than those with PD-L1 negative NSCLC (PD-L1 expression in less than 1% of tumor cells).
The most common (greater than or equal to 20%) grade 1-4 adverse reactions in the nivolumab arm included fatigue, musculoskeletal pain, cough, decreased appetite, and constipation. The most common (greater than or equal to 2%) grade 3-4 adverse reactions were dyspnea, fatigue, pneumonia, pulmonary embolism, pleural effusion, hyperglycemia, respiratory failure, and pain. The most common (greater than or equal to 2%) grade 3-4 laboratory abnormalities included lymphopenia, hyponatremia, anemia, increased AST, and increased ALT. 
Serious adverse events were reported in 47 of patients receiving nivolumab. The most common serious adverse events were pneumonia, pulmonary embolism, dyspnea, and pleural effusion. Immune-mediated adverse events that occurred in patients treated with nivolumab included hypothyroidism/thyroiditis, rash, pneumonitis, diarrhea/colitis, hyperthyroidism, hepatitis, nephritis, limbic encephalitis, and polymyalgia rheumatica.
The recommended dose and schedule for nivolumab is 3 mg/kg intravenously every two weeks.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125554s005lbl.pdf
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 by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Page Last Updated: 10/13/2015
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