Questions about Portrazza

Unmet need
What is the history of overall survival (OS) improvements in first-line squamous non-small cell lung cancer (NSCLC)?

Between 1970 and 1980 the median OS for patients with squamous NSCLC was approximately 2-5 months with best supportive care. Following the introduction of single-agent platinum therapy in the 1980s, OS improved to a median of 6-8 months. Then, as platinum-based doublets became the preferred therapy in the 1990s, median OS increased to 8-10 months. Since the introduction of platinum-based doublets, survival improvements for the majority of patients with squamous NSCLC have remained unchanged for 2 decades.

This lack of survival advancements in the first-line treatment of squamous NSCLC represents a high unmet need. Learn more here.

Patient types
Which of my patients might be eligible for treatment with Portrazza plus gemcitabine and cisplatin?

Portrazza® (necitumumab) is indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous NSCLC.

Limitation of Use: Portrazza is not indicated for treatment of nonsquamous NSCLC.

WARNING: CARDIOPULMONARY ARREST and HYPOMAGNESEMIA

  • Cardiopulmonary arrest and/or sudden death occurred in 3% of patients treated with Portrazza in combination with gemcitabine and cisplatin. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, with aggressive replacement when warranted during and after Portrazza administration
  • Hypomagnesemia occurred in 83% of patients receiving Portrazza in combination with gemcitabine and cisplatin, and was severe in 20% of patients. Monitor patients for hypomagnesemia, hypocalcemia, and hypokalemia prior to each dose of Portrazza during treatment and for at least 8 weeks following completion of Portrazza. Withhold Portrazza for grade 3 or 4 electrolyte abnormalities. Replete electrolytes as medically appropriate

For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.

Portrazza clinical trial
What was the SQUIRE trial?

The phase III trial evaluated the efficacy and safety of Portrazza plus gemcitabine and cisplatin vs gemcitabine and cisplatin first-line chemotherapy in patients with metastatic squamous NSCLC. Main outcome measure was OS. Supportive outcome (investigator-accessed) measures were PFS and ORR. All patients were required to have ECOG PS of 0, 1, or 2. Patients were randomized 1:1 to receive either Portrazza 800 mg IV on D1, D8 plus gemcitabine 1250 mg/m2 IV on D1, D8 and cisplatin 75 mg/m2 on D1, or gemcitabine 1250 mg/m2 IV on D1, D8 and cisplatin 75 mg/m2 on D1, q3w, for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients demonstrating at least stable disease on Portrazza plus gemcitabine and cisplatin were to continue Portrazza as a single agent in the absence of disease progression or unacceptable toxicity after completion of 6 planned courses of chemotherapy or if chemotherapy was discontinued for toxicity.

View the complete study design for SQUIRE here.

For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.

Efficacy
Is there an overall survival (OS) benefit with Portrazza plus gemcitabine and cisplatin?

Portrazza plus gemcitabine and cisplatin demonstrated a statistically significant improvement in OS compared with gemcitabine and cisplatin alone in the SQUIRE trial, where OS in the Portrazza arm was 11.5 months (95% confidence interval [CI]: 10.4, 12.6) vs 9.9 months (95% CI: 8.9, 11.1) in the gemcitabine and cisplatin arm, (hazard ratio [95% CI]: 0.84 [0.74, 0.96]; P=0.01]). The percentage of deaths at the time of analysis was 77% (418 patients) and 81% (442 patients) in the Portrazza plus gemcitabine and cisplatin and gemcitabine and cisplatin arms, respectively.

View the complete study design for SQUIRE here.

View complete SQUIRE OS data here.

For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.

Did Portrazza plus gemcitabine and cisplatin delay disease progression?

In addition to demonstrating a statistically significant improvement in overall survival (OS), Portrazza plus gemcitabine and cisplatin demonstrated a statistically significant improvement in progression-free survival (PFS) vs gemcitabine and cisplatin alone. PFS with Portrazza was 5.7 months (95% confidence interval [CI]: 5.6, 6.0) vs 5.5 months (95% CI: 4.8, 5.6) with gemcitabine and cisplatin alone (hazard ratio [95% CI]: 0.85 [0.74, 0.98]; P=0.02). The percentage of events at the time of analysis was 79% (431 patients) and 76% (417 patients) in the Portrazza plus gemcitabine and cisplatin and gemcitabine and cisplatin arms, respectively. ORR was also assessed and there was no difference between arms, with an ORR of 31% (95% CI: 27, 35) for the Portrazza plus gemcitabine and cisplatin arm and an ORR of 29% (95% CI: 25, 33) for the gemcitabine and cisplatin arm (P=0.40).

View a summary of the SQUIRE trial design here.

View both SQUIRE PFS and ORR data here.

For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.

Safety
What adverse reactions should I be aware of with Portrazza plus gemcitabine and cisplatin?

WARNING: CARDIOPULMONARY ARREST and HYPOMAGNESEMIA

  • Cardiopulmonary arrest and/or sudden death occurred in 3% of patients treated with Portrazza in combination with gemcitabine and cisplatin. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, with aggressive replacement when warranted during and after Portrazza administration
  • Hypomagnesemia occurred in 83% of patients receiving Portrazza in combination with gemcitabine and cisplatin, and was severe in 20% of patients. Monitor patients for hypomagnesemia, hypocalcemia, and hypokalemia prior to each dose of Portrazza during treatment and for at least 8 weeks following completion of Portrazza. Withhold Portrazza for grade 3 or 4 electrolyte abnormalities. Replete electrolytes as medically appropriate

The most common adverse reactions (all grades) observed in Portrazza-treated patients at a rate of ≥15% and ≥2% higher than gemcitabine and cisplatin alone were rash (44% vs 6%), vomiting (29% vs 25%), diarrhea (16% vs 11%), and dermatitis acneiform (15% vs 0.6%).

Adverse reactions (all grades; grade 3/4) that occurred at an incidence rate of ≥5% (all grades) or a ≥2% (grade 3/4) difference between patients receiving Portrazza plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in study 1 were rash (44% vs 6%; 4% vs 0.2%), dermatitis acneiform (15% vs 0.6%; 1% vs 0%), acne (9% vs 0.6%; 0.4% vs 0%), pruritus (7% vs 0.9%; 0.2% vs 0.2%), dry skin (7% vs 1%; 0% vs 0%), skin fissures (5% vs 0%; 0.4% vs 0%), vomiting (29% vs 25%; 3% vs 0.9%), diarrhea (16% vs 11%; 2% vs 1%), stomatitis (11% vs 6%; 1% vs 0.6%), weight decreased (13% vs 6%; 0.7% vs 0.6%), hemoptysis (10% vs 5%; 1% vs 0.9%), pulmonary embolism (5% vs 2%; 4% vs 2%), headache (11% vs 6%; 0% vs 0.4%), VTE (9% vs 5%; 5% vs 3%), paronychia (7% vs 0.2%; 0.4% vs 0%), and conjunctivitis (7% vs 2%; 0.4% vs 0%).

The most common severe (grade 3 or higher) adverse events that occurred at a ≥2% higher rate in Portrazza-treated patients compared to patients treated with gemcitabine and cisplatin alone were VTE (5%; including pulmonary embolism), rash (4%), and vomiting (3%).

Clinically relevant adverse reactions (all grades) reported in ≥1% and <5% of patients treated with Portrazza were dysphagia (3%), oropharyngeal pain (1%), muscle spasms (2%), phlebitis (2%), and hypersensitivity/IRRs (1.5%).

In study 1, 12% of the patients in the Portrazza arm discontinued study treatment due to an adverse reaction. The most common Portrazza-related toxicity leading to Portrazza discontinuation was skin rash (1%).

Electrolyte abnormalities (all grades; grade 3 or 4) according to laboratory assessment at an incidence rate of >10% and a >2% difference between arms in patients receiving Portrazza plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in study 1 included hypomagnesemia (83% vs 70%; 20% vs 7%), hypokalemia (28% vs 18%; 5% vs 3%), hypocalcemia (45% vs 30%; 6% vs 2%), albumin corrected hypocalcemia (36% vs 23%; 4% vs 2%), and hypophosphatemia (31% vs 23%; 8% vs 6%).

The median time to onset of hypomagnesemia was 6 weeks (25th percentile 4 weeks; 75th percentile 9 weeks). Hypomagnesemia was reported as resolved in 43% of the patients who received Portrazza. In study 1, 32% of the patients in the Portrazza arm and 16% of the patients who received gemcitabine and cisplatin alone received magnesium replacement.

View the adverse reaction profile for Portrazza plus gemcitabine and cisplatin here.

For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.

Dosing
What is the recommended dose for Portrazza? Are there any premedications or concurrent medications that must be administered with Portrazza?

The recommended dose of Portrazza is 800 mg administered as an intravenous infusion over 60 minutes on Days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion.

Portrazza is first administered in combination with gemcitabine and cisplatin for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients demonstrating at least stable disease on Portrazza plus gemcitabine and cisplatin were to continue Portrazza as a single agent in the absence of disease progression or unacceptable toxicity after completion of 6 planned courses of chemotherapy or if chemotherapy was discontinued for toxicity.

  • For patients who have experienced a previous grade 1 or 2 infusion-related reaction (IRR), premedicate with diphenhydramine hydrochloride (or equivalent) prior to all subsequent Portrazza infusions
  • For patients who have experienced a second grade 1 or 2 occurrence of IRR, premedicate for all subsequent infusions, with diphenhydramine hydrochloride (or equivalent), acetaminophen (or equivalent), and dexamethasone (or equivalent) prior to each Portrazza infusion
  • See gemcitabine and cisplatin prescribing information for recommended dosage and premedications

View the recommended dose and schedule for Portrazza, including premedication instructions, here.

For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.

Mechanism of action
How does Portrazza inhibit epidermal growth factor receptor (EGFR)–mediated tumor activity?

Portrazza is a recombinant human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. Binding of Portrazza induces EGFR internalization and degradation in vitro. In vitro, binding of Portrazza also led to antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells.

Portrazza in combination with gemcitabine and cisplatin has demonstrated antitumor activity in an in vivo animal model of NSCLC.

Learn more about the mechanism of action of Portrazza here.

For safety and dosing guidelines, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.