Science in the News
Another Novel Immunomodulatory Biologic Agent, Nivolumab (Opdivo®), Gains Additional Approval for Use in Patients with Advanced Head and Neck Cancer
November 11, 2016
On November 10, 2016,1, 2
the U.S. Food and Drug Administration (FDA) granted accelerated approval for a new indication for the humanized monoclonal antibody biologic agent, nivolumab (Opdivo®
, Bristol-Myers Squibb Co.) for use in recurrent/metastatic squamous-cell head and neck cancer (HNSCC) that has advanced during or is unresponsive to platinum-containing chemotherapy.2
Another related biologic agent, pembrolizumab (Keytruda®
) was FDA approved for the same supplemental indication on August 5, 2016.3-5
Nivolumab has been previously FDA approved, both as single-agent and as combination therapy for unresectable/metastatic melanoma; for a specific type of metastatic nonsmall-cell lung cancer that has progressed during or after platinum-containing chemotherapy; for advanced renal cancer following previous antiangiogenic therapy; and for classical Hodgkin lymphoma that has relapsed or progressed following autologous stem-cell transplant and post-transplant brentuximab vedotin.2
The approved dose schedule for recurrent/metastatic HNSCC is 3 mg/kg IV (administered as an infusion over 60 minutes) every 2 weeks.2
are humanized immunoglobulin (IgG4/kappa) monoclonal antibodies that bind an inhibitory signaling receptor expressed on the surface of activated T-cells called “programmed (cell) death-1” or “PD-1.” PD-1 ligands overexpressed on certain cancer cells can activate the inhibitory properties of PD-1 receptors, allowing cancer cells to go unrecognized by T-cells. By blocking the PD-1 receptor-ligand binding, these biologics act to stimulate the body’s immune system, allowing it to play a bigger role in cancer cell recognition and destruction.7, 8
Approval was based on data from an international, multicenter, open-label, randomized trial called “CheckMate 141,” which compared nivolumab with investigator choice of chemotherapy (either cetuximab, methotrexate, or docetaxel) in patients with recurrent or metastatic HNSCC with disease progression on or within 6 months of receiving platinum-based chemotherapy.1, 2
Checkmate 141 enrolled 361 patients randomized in a 2:1 ratio to nivolumab 3 mg/kg IV every 2 weeks (n=240) or investigator choice of chemotherapy regimen (n=121), either cetuximab (n=15), methotrexate (n=52), or docetaxel (n=54), until disease progression or unacceptable toxicity.1, 2
The trial demonstrated a statistically significant and clinically meaningful improvement in overall survival associated with the nivolumab arm (Hazard Ratio [HR] 0.7; 95% confidence interval [CI]: 0.52, 0.92; p=0.0101 by stratified log rank test). Estimated median overall was 7.5 months (95% CI: 5.5, 9.1) in the nivolumab arm and 5.1 months (95% CI: 4, 6.0) in the chemotherapy-treated arm.1, 2
Serious adverse reactions occurred in 49% of the patients receiving nivolumab. The most frequent serious adverse reactions reported in at least 2% of patients receiving the agent were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. The most common adverse reactions occurring in more than 10% of nivolumab-treated patients and at a higher incidence than chemotherapy-treated patients were cough and dyspnea. The most common laboratory abnormalities occurring in 10% or more nivolumab-treated patients and at a higher incidence than chemotherapy-treated patients were increased alkaline phosphatase, increased amylase, hypercalcemia, hyperkalemia, and increased thyroid-stimulating hormone.1, 2
- U.S. Food and Drug Administration. FDA Approved Drugs: Nivolumab for SCCHN. Accessed November 10, 2016.
- Bristol-Myers Squibb Co. Opdivo (nivolumab) injection, for intravenous use (rev. 11/2016). Accessed November 10, 2016.
- Merck & Co. Inc.. Keytruda (pembrolizumab) for injection/injection, for intravenous use (rev. 8/2016). Accessed August 10, 2016.
- U.S. Food and Drug Administration. FDA Approved Drugs: pembrolizumab (KEYTRUDA). Accessed August 10, 2016.
- American Dental Association. Science in the News: A Novel Immunomodulatory Biologic Agent, Pembrolizumab (Keytruda®), Gains Additional Approval for Use in Patients with Advanced Head and Neck Cancer (posted August 18, 2016). Accessed November 10, 2016.
- National Cancer Institute (NCI). NCI Drug Dictionary: Nivolumab. Accessed November 10, 2016.
- National Cancer Institute (NCI). NCI Drug Dictionary: Pembrolizumab. Accessed November 10, 2016.
- Machiels JP, Coulie PG. The promise of immunostimulatory antibodies in head and neck cancer. Lancet Oncol 2016;17(7):856-7.
Prepared by: Center for Scientific Information, ADA Science Institute
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