Mechanism of Action

Portrazza (necitumumab) is a recombinant human lgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. Expression and activation of EGFR has been correlated with malignant progression, induction of angiogenesis and inhibition of apoptosis. Binding of necitumumab induces EGFR internalization and degradation in vitro. In vitro, binding of necitumumab also led to antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells.

Side Effects

Adverse effects associated with the use of Portrazza may include, but are not limited to, the following:

Rash

Hypomagnesemia

Portrazza comes with a boxed warning regarding the risk of cardiopulmonary arrest and hypomagnesemia.

Dosing/Administration

Portrazza is supplied as a solution for intravenous administration. The recommended dose is 800 mg administered as an intravenous infusion over 60 minutes on Days 1 and 8 of each three-week cycle prior to gemcitabine and cisplatin infusion. Continue until disease progression or unacceptable toxicity.

Please see drug label for specific dose modifications.

Clinical Trial Results

FDA Approval

The FDA approval of Portrazza was based on SQUIRE, an open-label, randomized, multicenter phase 3 trial that compared first-line treatment with Portrazza in combination with gemcitabine and cisplatin to treatment with gemcitabine and cisplatin alone in 1,093 patients with metastatic squamous NSCLC. Patients on both arms of the study were allowed to receive a maximum of six cycles of chemotherapy. Patients on the Portrazza arm demonstrating at least stable disease continued to receive additional cycles of Portrazza until disease progression or unacceptable toxicity. Results showed a statistically significant improvement in overall survival over gemcitabine and cisplatin alone, specifically in the first-line setting. Portrazza combination therapy showed a statistically significant improvement in overall survival, the main outcome measure (p=0.01), with a median overall survival of 11.5 months for the Portrazza arm, as compared to 9.9 months for those treated with gemcitabine and cisplatin alone. This translated to a 16 percent reduction in risk of death. The percentage of deaths at the time of analysis was 77 percent on the Portrazza arm and 81 percent on the control arm. The significant survival improvement observed in SQUIRE was supported by a statistically significant improvement in progression-free survival (p=0.02), with a median progression-free survival (PFS) of 5.7 months on the Portrazza arm, as compared to 5.5 months for those treated with gemcitabine and cisplatin alone. The percentage of events at the time of analysis was 79 percent on the Portrazza arm and 76 percent on the control arm. Overall response rate (ORR) was also assessed and there was no difference between arms, with an ORR of 31 percent for the Portrazza plus gemcitabine and cisplatin arm and an ORR of 29 percent for the gemcitabine and cisplatin arm (p=0.40).