FDA approves tarceva for the treatment of non-small cell lung cancer
FDA has approved Tarceva (Erlotinib) for the treatment of advanced non-small cell lung cancer, a pill to treat lung cancer. The approval by the FDA came well before the agency's late-January deadline, making it one of the fastest drug approvals ever.
Tarceva was approved for patients with advanced non-small cell lung cancer, who have failed to respond to at least one prior round of chemotherapy. Previously a similar drug Gefitinib (Iressa) by AstraZeneca was approved for the same indication (non-small cell lung cancer) but it was later shown in a large study that the drug does not increase survival. Gefitinib is non longer an active option for non-small cell lung cancer patients. Tarceva has shown to prolong life in in patients with non-small cell lung cancer a clinical trials by a median of 6.7 months compared to 4.7 months for patients who got a placebo. So far, Iressa has only been shown to shrink tumors.
These drugs, so-called targeted drugs tend to have fewer side effects than conventional chemotherapy. The main side effects of Tarceva are a skin rash and diarrhea, although there have been infrequent reports of serious or even fatal lung disease in patients taking the drug. Other drugs used in similar setting of second line treatment of non-small cell lung cancer include Alimta from Eli Lilly and Taxotere from Aventis, and both of these drugs are approved for second treatments of non-small cell lung cancer.
Tarceva, a pill taken once a day, will be priced at slightly more than $2,000 wholesale for a month's supply, said Colin Goddard, chief executive of OSI.
Patients and doctors have complained recently about the high prices of cancer drugs. Dr. Goddard defended the price of Tarceva, saying it was "set competitively against the other drugs in play." He said the drug was priced at a few hundred dollars more per month than Iressa but less than many other cancer drugs.
In another clinical trial, Tarceva was found to extend the lives of patients with pancreatic cancer, which is extremely difficult to treat. The companies plan to apply for approval for that use next year, Dr. Goddard said.
OSI initially came up with the drug, and licensed marketing rights to Genentech and Roche, the Swiss company that owns a majority of Genentech. Genentech, with help from OSI, will sell the drug in the United States for patients with non-small cell lung cancer, while Roche will handle sales overseas. Approval Europe for non-small cell lung cancer is expected around the middle of 2005.
Tarceva is the fourth Genentech drug - and the second one for cancer - approved in the last two years.
Results from two multi-center, placebo controlled, randomized clinical trials conducted in first line patients with locally advanced or metastatic non-small cell lung cancer have shown no clinical benefit with the concurrent administration of Tarceva with platinum based (cisplatin or carboplatin) chemotherapy. Tarceva should not be given with chemotherapy.
Key features about Tarceva and the clinical trial that led to the approval of Tarceva in non-small cell lung cancer
More on Tarceva
- Tarceva is Her1/EGFR targeted therapy and inhibits tyrosine kinase phosphorylation
- The efficacy and safety of Tarceva were assessed in a randomized, double-blinded, placebo-controlled trial in 731 patients with locally advanced or metastatic non-small cell lung cancer
- All patients had failure of at least one prior chemotherapy regimen
- Patients were randomized 2:1 to receive Tarceva 150 mg or placebo (488 Tarceva, 243 placebo) orally once daily until disease progression or unacceptable toxicity.
- Study endpoints included overall survival, response rate and Progression-Free Survival (PFS).
- The study was conducted in 17 countries.
- Tarceva prolongs overall survival compared to placebo (6.7 months Vs 4.7months)
- Tarceva increases one-year survival (31.2% Vs 21.5%)
- Tarceva increases progression free survival (9.9 weeks Vs 7.9 weeks)
- Prolongs survival in EGFR positive non-small cell lung cancer patients (10.7months Vs 3.8 months)
- Tarceva had no survival effect on EGFR negative patients
- Monitor liver function tests while on treatment
- Monitor for interstitial lung disease while on treatment
- Recommended dose: 150 mg tabs once daily orally between meals (at least 1 hour before or 2 hours after eating)
- Doses above 150mg may cause unacceptable degree of side effects (diarrhea, rash and liver enzyme elevation)
- Treatment should be continued till disease progression or unacceptable toxicity
- Tarceva is available as 150mg, 100mg, and 25mg tablets
- Dose reduction should be considered in cases of intolerable skin reactions, diarrhea that is unresponsive to Imodium, severe live function abnormalities
- When dose reduction is required decrease in decrements of 50mg
- In the phase III trial 6% and 1% of patients needed dose reduction for rash and diarrhea respectively
- There have been infrequent reports of serious Interstitial Lung Disease (ILD), including fatalities, in patients receiving Tarceva for treatment of non-small cell lung cancer or other advanced solid tumors.
- In the randomized, Phase III, single-agent study, the incidence of ILD (0.8%) was the same in both the placebo and Tarceva groups. The overall incidence in Tarceva-treated patients from all studies (including uncontrolled studies and studies with concurrent chemotherapy) was approximately 0.6%.
- In the event of acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough and fever, Tarceva therapy should be interrupted pending diagnostic evaluation.
- If ILD is diagnosed, Tarceva should be discontinued permanently and appropriate treatment instituted as necessary.
- Ketoconazole, atazanavir, clarithromycin, indinavir, itrconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telehromycin, troleandomycin and voriconazole increases the drug level of Tarceva
- Tarceva may increase INR and may cause GI bleeding. Patients taking warfarin should be monitored for changes in INR
- Conjectivitis, keratitis and corneal ulcerations may occur
- Other side effects: anorexia, fatigue, dyspnea, cough, nausea, infection, vomiting, stomatitis, prutitis, dry skin, abdominal pain
Phase III trial for tarceva (Erlotinib) in non-small cell lung cancer
Tarceva (Erlotinib) improves survival in advanced pancreatic cancer