FDA Approves Lung Cancer Drug

By Dr Deepu

The Wall Street Journal (11/25, B6, Steele, Subscription Publication) reports that the Food and Drug Administration announced Tuesday that it had approved Eli Lilly’s lung cancer drug, Portrazza (necitumumab). Portrazza, in combination with two forms of chemotherapy, treats patients who have advanced squamous non-small cell lung cancer and have not already received another treatment for their advanced lung cancer.

        The Indianapolis Star (11/25, Swiatek) reports that the drug “is the first biologic approved to treat patients with metastatic squamous non-small-cell lung cancer.” Although Eli Lilly did not release a price for the drug, the company “said it plans to offer a discount program to offer income-eligible patients a way to receive Portrazza for a copay of no more than $25 a dose.” 

Indicated for first-line treatment of metastatic squamous NSCLC in combination with gemcitabine and cisplatin

800 mg IV infused over 1 hr on days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion

Continue therapy until disease progression or unacceptable toxicity.

Mechanism of Action
Epidermal growth factor receptor (EGFR) inhibitor; monoclonal antibody that binds to the human EFGR and blocks interaction between EGFR and its ligands
Expression and activation of EGFR has been correlated with malignant progression, induction of angiogenesis, and inhibition of apoptosis
Pharmacokinetics
Time to steady state: ~100 days
Total systemic clearance at steady-state: 14.1 mL/hr
Vd: 7 L
Half-life: ~14 days

Adverse effects

Infusion-related reactions

1. Grade 1: Reduce the infusion rate by 50%
2. Grade 2: Stop the infusion until signs and symptoms have resolved to grade 0 or 1; resume infusion at 50% reduced rate for all subsequent infusions
3. Grade 3 or 4 IRR: Permanently discontinue

Dermatologic toxicity

·         Grade 3 rash or acneiform rash: Withhold until symptoms resolve to grade ≤2, then resume infusion at reduced dose of 400 mg for at least 1 treatment cycle; if symptoms do not worsen, may increase dose to 600 mg and 800 mg in subsequent cycles

·         Permanently discontinue if

1. Grade 3 rash or acneiform rash do not resolve to grade ≤2 within 6 wk
2. Reactions worsen or become intolerable at a dose of 400 mg
3. Patient experiences grade 3 skin induration/fibrosis
4. Grade 4 dermatologic toxicity

Limitations of use: Not indicated for treatment of nonsquamous NSCLC

Hypomagnesemia (83%)

Hypocalcemia (45%)

Rash (44%)

Hypocalcemia (albumin corrected) (36%)

Hypophosphatemia (31%)

Vomiting (29%)

Hypokalemia (28%)

Hypomagnesemia, grade 3-4 (20%)

Diarrhea (16%)

Dermatitis acneiform (15%)

Weight decreased (13%)

Stomatitis (11%)

Headache (11%)

1-10%

Hemoptysis (10%)

Venous thromboembolic events (9%)

Acne (9%)

Hypophosphatemia, grade 3-4 (8%)

Paronychia (7%)

Conjunctivitis (7%)

Pruritus (7%)

Dry skin (7%)

Hypocalcemia, grade 3-4 (6%)

Hypokalemia, grade 3-4 (5%)

Skin fissures (5%)

Pulmonary embolism (5%)

Venous thromboembolic events, grade 3-4 (5%)

Hypocalcemia (albumin corrected), grade 3-4 (4%)

Vomiting, grade 3-4 (3%)

Diarrhea, grade 3-4 (2%)