Tarceva shown to extend survival in advanced non-small cell lung cancer when used after initial chemo

OSI Pharmaceuticals, Inc. has announced further results from the Phase III SATURN study showing that Tarceva® (erlotinib) extended the survival of patients with advanced non-small cell lung cancer (NSCLC) when used as single agent, maintenance therapy in patients who did not progress following first-line treatment with platinum-based chemotherapy.

As previously announced, the safety results in this study were consistent with what has been seen previously and there were no new or unexpected safety signals. Overall survival was a key secondary endpoint of the study and these new data were presented today at the 13th World Conference on Lung Cancer being held in San Francisco.

"Based on the data presented today, Tarceva is the first oral cancer therapy to show a survival benefit in the first-line maintenance NSCLC setting. Assuming approval, when used immediately after chemotherapy, Tarceva will provide a new, convenient, non-chemotherapy treatment option for patients - allowing doctors to continue treating a patient's disease without exposing them to the continuous burden and lifestyle constraints of long-term chemotherapy," stated Gabe Leung, President, Pharmaceutical Business of OSI Pharmaceuticals.

The study showed that patients with NSCLC treated with Tarceva had a 23 percent improvement in overall survival compared with patients who received placebo (hazard ratio=0.81; p-value=0.0088). The hazard ratio, which assesses risk in the overall trial population, is widely recognized as the best measure of overall benefit in large randomized clinical trials. A hazard ratio of less than one for survival indicates a reduced risk of death. The median survival (a single point estimate of benefit) for patients receiving Tarceva was 12 months versus a median survival of 11 months for patients receiving placebo.

The study confirmed that a broad spectrum of patients with advanced NSCLC experienced a survival benefit from Tarceva. Specific analysis of patients in the study whose tumors were confirmed not to have genetic mutations in their epidermal growth factor receptor (EGFR "wild-type") showed that this group experienced a 30 percent improvement in survival (hazard ratio = 0.77; p-value = 0.0243). The majority of patients with NSCLC are EGFR wild-type. Full data analysis for various sub-groups is still on-going. However, available data also showed that the hazard ratio for overall survival in patients with tumors expressing the EGFR gene by Immunohistochemistry (IHC) was also 0.77 (p-value = 0.0063).

As presented previously, the hazard ratio for progression-free survival (the time patients live without their disease worsening) in patients with EGFR mutations was 0.10 (p-value <0.0001). Overall survival for this patient sub-group is still immature with the median survival not yet being reached in patients with EGFR mutations receiving Tarceva. Determination of the overall survival benefit in this sub-group was further confounded by the fact that two-thirds of the patients with EGFR mutations who received placebo crossed over to receive Tarceva or another EGFR therapy. An ongoing Phase III trial evaluating how Tarceva compared to traditional chemotherapy for first-line treatment in patients whose tumors had an EGFR mutation is expected to provide more insight. This study, called EURTAC, is a collaboration between Roche and the Spanish Lung Cancer Group.

"The overall SATURN results continue to reinforce our belief that Tarceva therapy for NSCLC patients whose cancers have an EGFR mutation has the potential to result in a major advancement in personalized medicine using targeted therapies - even as they continue to demonstrate the broad-based benefit of Tarceva therapy in treating the overall NSCLC population," stated David Epstein, Senior Vice President, Oncology Research at OSI Pharmaceuticals.

Additional analysis on survival in other patient subsets and in patients with specific biomarkers is still on-going and will be presented at future meetings.

The overall survival data will be submitted to the U.S. Food and Drug Administration (FDA) to support the supplemental New Drug Application (sNDA) for use of Tarceva as a first-line maintenance treatment for patients with advanced NSCLC that was submitted on March 17, 2009. The FDA Prescription Drug User Fee Act (PDUFA) review date will be on or about January 18, 2010. Additionally, Roche, OSI's international collaborator for Tarceva, will submit the overall survival data to the European Medicines Agency (EMEA) to support the application for use of Tarceva as a first-line maintenance treatment submitted in March 2009.

SATURN is an international, placebo-controlled, randomized, double-blind, Phase III study conducted by Roche 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 were then randomized to Tarceva or placebo if the cancer did not progress.

The study met its primary endpoint and showed patients with advanced NSCLC who received Tarceva as a first-line maintenance treatment had a 41 percent improvement in the time they lived without the disease advancing (progression-free survival or PFS) compared to placebo (hazard ratio=0.71). PFS was defined as the length of time from randomization to disease progression or death from any cause. The co-primary endpoint was PFS in patients with EGFR-positive tumors by IHC. Secondary endpoints included overall survival, safety and an evaluation of exploratory biomarkers, including EGFR mutations and K-ras mutations.

The safety results were consistent with what has been previously seen and there were no new or unexpected safety signals in the study. The most commonly reported adverse events in patients who received Tarceva were rash (49 percent, 213/438) and diarrhea (20 percent, 88/438).



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