General Information

Tarceva (erlotinib) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. While the complete mechanism of action is not entirely understood, the drug appears to impede cell-cell signaling pathways, which have been implicated in rapid cell division and survival. Overactivation of these pathways is thought to be central to tumor growth and metastasis.

It is specifically indicated as monotherapy to treat non-small cell lung cancer in patients who have failed to respond or has ceased responding to at least one round of chemotherapy. It is not indicated as a first-line therapy. Results from two, multicenter, placebo-controlled, randomized, phase 3 trials conducted in first-line patients showed no clinical benefit with the concurrent administration of Tarceva with platinum-based chemotherapy regimens.

Mechanism of Action

Tarceva (erlotinib) is a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. While the complete mechanism of action is not entirely understood, the HER1 and EGFR receptors are directly involved in inter-cellular signaling in systems governing cell division and proliferation. By inhibiting the function of these receptors, which are highly active and often over-expressed in rapidly dividing tumor cells, Tarceva is thought to limit tumor cells' ability to divide and metastasize and may help to initiate pathways of apoptotic cell death.

Side Effects

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

Rash

Diarrhea

Anorexia

Stomatitis

Pruritus

Infection

In addition to these events, infrequent serious interstitial lung disease (ILD) has been observed, including fatalities. ILD incidence in the trial which formed the basis of FDA approval was the same for both placebo and Tarceva groups (0.8 percent of patients). Most cases were associated with confounding or contributing factors. Tarceva use should be suspended pending evaluation on the appearance of new pulmonary symptoms and discontinued upon diagnosis of ILD.

Dosing/Administration

Tarceva is administered as an oral tablet, with a recommended dosage of 150 mg once daily at least one hour before or two hours after eating. Patients experiencing significant adverse reactions should reduce dosage as appropriate in 50 mg decrements.

Clinical Trial Results

FDA approval of Tarceva was a double-blind, placebo-controlled clinical studies enrolling a combined total of 731 subjects with confirmed locally advanced or metastatic NSCLC after failure of at least one chemotherapy regimen. The trial randomized subjects at a 2:1 ratio to receive Tarceva (n=488) or placebo (n=243) orally once daily until evidence of disease progression or unacceptable toxicity. In the intent to treat population, Tarceva was found to significantly improve one-year survival time, progression-free tumor response and response duration and median overall response duration. In subsets of patients with EGFR- positive tumors and patients who never smoked, the drug appeared to carry improved efficacy.

Results from two, multicenter, placebo-controlled, randomized trials in over 1,000 patients investigating the drug as a first-line adjuvant to standard platinum-based chemotherapy regimens (carboplatin and paclitaxel or gemcitabine and cisplatin) indicated that patients with locally advanced or metastatic NSCLC showed no clinical benefit in terms of tumor response or survival benefit with the concurrent administration of TARCEVA versus chemotherapy alone.