Τετάρτη, 25 Νοεμβρίου 2015

FDA APPROVED NICITUMUMAB FOR SQUAMOUS NSCLC

The U.S. Food and Drug Administration today approved necitumumab (Portrazza) in combination with gemcitabine and cisplatin for first-line treatment of patients with metastatic squamous non–small cell lung cancer (NSCLC). Necitumumab is not indicated for treatment of nonsquamous NSCLC.
Necitumumab is a recombinant human IgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands.
Clinical Trial Results
Approval was based on the results of an open-label, multicenter, multinational, randomized trial of necitumumab in combination with gemcitabine and cisplatin vs gemcitabine and cisplatin alone in in patients with metastatic squamous NSCLC who had not received prior therapy for metastatic disease (N = 1,093). Patients received necitumumab at 800 mg by intravenous infusion on days 1 and 8, gemcitabine at 1,250 mg /m2 on days 1 and 8 plus cisplatin at 75 mg/m2 on day 1 of each 3-week cycle (N = 545) or gemcitabine/cisplatin alone (N = 548). 
The major efficacy outcome was overall survival. Progression-free survival and overall response rate were also assessed.
Necitumumab in combination with gemcitabine/cisplatin demonstrated a statistically significant improvement in overall and progression-free survival as compared with gemcitabine/cisplatin alone. Median overall survival was 11.5 months (95% confidence interval [CI] = 10.4–12.6) for patients assigned to necitumumab plus gemcitabine/cisplatin and 9.9 months (95% CI = 8.9–11.1) for those assigned to gemcitabine/cisplatin alone (hazard ratio [HR] = 0.84, 95% CI  = 0.74–0.96, = .01). Median progression-free survival was 5.7 months for patients assigned to necitumumab plus gemcitabine/cisplatin and 5.5 months for those assigned to gemcitabine/cisplatin alone (HR = 0.85, 95% CI = 0.74–0.98, = .02). 
No difference in overall response rate between arms was observed, with an overall response rate of 31% (95% CI = 27–35) for necitumumab plus gemcitabine/cisplatin and 29% (95% CI = 25–33) for gemcitabine/cisplatin alone, (= .40).
Side Effects
The most common adverse reactions (all grades) observed in necitumumab-treated patients at a rate of greater than or equal to 30% and greater than or equal to 2% higher than the gemcitabine/cisplatin–alone arm were rash and hypomagnesemia. Serious and clinically significant adverse events included hypomagnesemia, venous and arterial thromboembolic events, dermatologic toxicities, infusion reactions, and increased toxicity and increased mortality in patients with nonsquamous NSCLC. Death attributed to cardiovascular events or sudden death was reported in 3% of the patients in the necitumumab plus gemcitabine/cisplatin arm. 
Health-care providers should closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after necitumumab administration. Necitumumab should be withheld for grade 3 or 4 electrolyte abnormalities. 

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