OSI Pharmaceuticals and Genentech announced that FDA ( Food and Drug Administration ) Oncologic Drugs Advisory Committee ( ODAC ) voted 12 to one recommending against approval of Tarceva ( Erlotinib ) for first-line maintenance use in people with advanced or metastatic non-small cell lung cancer ( NSCLC ) whose cancer has not progressed following first-line treatment with Platinum-based chemotherapy.

The ODAC recommendation was based on a review of data from the pivotal Phase III SATURN study which showed a statistically significant improvement in both progression-free survival ( PFS ) and overall survival ( OS ) with Tarceva compared to placebo in the NSCLC maintenance setting.
There were no new or unexpected safety signals in the study and adverse events were consistent with those previously reported for Tarceva in NSCLC.

• Patients who received Tarceva had a 41 percent improvement in the likelihood of living without the disease getting worse ( PFS, the primary endpoint ) compared to placebo ( hazard ratio, HR=0.71, 29 percent reduction in the risk of cancer progression or death, p<0.0001; median PFS 12.3 weeks vs. 11.1 weeks ).

• Patients whose tumors over-expressed the epidermal growth factor receptor ( EGFR ) who received Tarceva had a 45 percent improvement in PFS compared to placebo ( the co-primary endpoint; HR=0.69, 31 percent reduction in the risk of cancer progression or death, p<0.0001; median PFS 12.3 weeks vs. 11.1 weeks ).

• Overall survival, a key secondary endpoint, was also significantly improved by 23 percent with Tarceva compared to placebo ( HR=0.81, 19 percent reduction in the risk of death, p=0.0088; median OS 12.0 months vs. 11.0 months ).

• The most commonly reported adverse events in patients who received Tarceva were rash ( 49 percent ) and diarrhea ( 20 percent ). Grade 3 rash and diarrhea were experienced by six percent and two percent of patients, respectively. There were no cases of grade 4 rash or diarrhea.

SATURN was an international, placebo-controlled, randomized, double-blind, Phase III study that enrolled 889 patients with advanced NSCLC at approximately 160 sites worldwide. Patients were treated with four cycles of standard first-line platinum-based chemotherapy and then randomized to Tarceva or placebo if the cancer did not progress. The co-primary endpoints were PFS in all patients and PFS in patients whose tumors over-expressed EGFR.
Progression-free survival was defined as the length of time from randomization to disease progression or death from any cause. Secondary endpoints included overall survival, safety and an evaluation of exploratory biomarkers.

Tarceva is a monoclonal antibody that targets the EGFR pathway. Tarceva is designed to inhibit the tyrosine kinase activity of the EGFR signaling pathway inside the cancer cell, one of the critical growth factors in NSCLC and pancreatic cancer.
Tarceva is indicated as a monotherapy for patients with locally advanced or metastatic NSCLC whose disease has progressed after one or more courses of chemotherapy.
Tarceva is not intended to be used at the same time as chemotherapy for NSCLC.
In pancreatic cancer, Tarceva is indicated in combination with Gemcitabine chemotherapy for the first-line treatment of patients with locally advanced pancreatic cancer, pancreatic cancer that cannot be surgically removed or pancreatic cancer that has spread to distant body organs.

There have been infrequent reports of serious interstitial lung disease (ILD)-like events including deaths in patients taking Tarceva. Serious side effects ( including deaths ) in patients taking Tarceva include liver and/or kidney problems; gastrointestinal perforations, and severe blistering skin reactions including cases similar to Stevens-Johnson syndrome.
Patients taking Tarceva plus Gemcitabine were more likely to experience bleeding and clotting problems such as myocardial infarction or stroke.
Eye irritation and damage to the cornea have been reported in patients taking Tarceva.
Women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva.
Patients should call their doctor right away if they have these signs or symptoms: new or worsening skin rash; serious or ongoing diarrhea, nausea, loss of appetite, vomiting or stomach pain; new or worsening shortness of breath or cough; fever; eye irritation.
Rash and diarrhea were the most common side effects associated with Tarceva in the NSCLC clinical study. Fatigue, rash, nausea, loss of appetite and diarrhea were the most common side effects associated with Tarceva plus Gemcitabine therapy in the pancreatic cancer clinical study.

Source: OSI Pharmaceuticals, 2009

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