Blood test helps target Roche/OSI lung cancer drug

Testing for specific cancer protein markers in lung cancer patients' blood helps find those more likely to respond to Tarceva, a drug sold by Roche and OSI Pharmaceuticals , data showed on Friday.

A study presented at the European Lung Cancer Conference in Geneva showed that a relatively simple blood analysis known as a proteomic test can identify patients whose tumours are likely to shrink with the drug -- one of a class called EGFR-blockers.

"The bottom line is that the proteomic test -- comparing 'good' and 'poor' profiles -- was strongly prognostic," David Carbone from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, who led the study, said in a statement.

"Proteomics 'good' patients also had a significantly higher response rate than proteomics 'poor' patients."

Tarceva, known generically as erlotinib, is sold by OSI and Roche and is designed to block EGFR, a gene that is overactive in many types of cancer cells.

Other drugs in the same class include AstraZeneca's lung cancer medicine Iressa, and colon cancer drugs Vectibix from Amgen and Erbitux -- sold by Bristol-Myers Squibb , Eli Lilly and Merck KGaA .

Lung cancer is the biggest cancer killer around the world, killing 1.2 million people a year. Only 15 percent of people diagnosed with lung cancer are still alive five years later.

Patients can already be tested to see if they have the right type of genetic profile to respond well to EGFR-blocking drugs, but the methods involve gene sequencing, which is complex and expensive, or a technique called fluorescence in-situ hybridization (FISH), which requires a sample of tumour tissue.

Carbone said FISH was a better predictor of benefit for Tarceva, but noted it can only be done with enough of a tissue sample.

In this study, tumour samples were only available in 22 percent of patients, he said, while 99 percent of patients were able to be successfully assessed with the proteomic test. "This (proteomic) test ... may be of particular value for those in whom tumour tissue is inadequate or unavailable," Carbone said.

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New Data from Phase III SATURN Study Showed Tarceva Improved Overall Survival When Used Immediately After Initial Chemotherapy in Patients with Advanc

OSI Pharmaceuticals, Inc. and Genentech, Inc. today announced that SATURN, a pivotal Phase III study of Tarceva® (erlotinib), met a key secondary endpoint of extending overall survival in patients with advanced non-small cell lung cancer (NSCLC) who received Tarceva immediately after initial chemotherapy. A statistically significant improvement in overall survival was seen in this pre-planned final analysis of the total patient population. The new data will be presented during the 13th World Conference on Lung Cancer to be held July 31 to August 4, 2009 in San Francisco.

Treating patients immediately following first-line chemotherapy versus waiting for the cancer to grow or spread before giving additional treatment represents a new approach in advanced NSCLC.

“This study has now not only confirmed that immediate treatment with Tarceva after initial chemotherapy delayed the progression of disease, but also importantly helped patients in the study live longer,” said Professor Federico Cappuzzo, M.D., Istituto Clinico Humanitas IRCCS, Milan and principal investigator of the SATURN study. “This is good news for doctors and their patients since advanced lung cancer is one of the most challenging cancers to treat and is often associated with a very short life expectancy.”

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.

The U.S. and EU submissions were based on positive data from SATURN that were presented at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) on May 31, 2009 in Orlando, Fla. SATURN 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; 29 percent reduction in the risk of cancer progression or death). The safety results were consistent with what has been seen previously 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).

According to the American Cancer Society, lung cancer is the leading cause of cancer death in the United States. In 2009, approximately 159,000 Americans will die from the disease. Most people are diagnosed with advanced stage disease and only 15 percent survive five years.

Source : www.drugs.com

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OSI Pharmaceuticals Announces Acceptance Of Tarceva Supplemental New Drug Application For Review By The U.S. Food And Drug Administration

OSI Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and review the supplemental New Drug Application (sNDA) for the use of Tarceva® (erlotinib) as a first-line maintenance treatment for patients with advanced non-small cell lung cancer (NSCLC) who have not progressed following first-line treatment with platinum-based chemotherapy. Based upon the March 17th receipt of filing the FDA Prescription Drug Fee Act (PDUFA) review date will be on or about January 18, 2010.

"We are pleased with the FDA's decision to review the data to evaluate Tarceva as a first-line maintenance therapy," stated Colin Goddard, Ph.D., Chief Executive Officer of OSI Pharmaceuticals. "This decision puts us one step closer toward accomplishing our goal of making Tarceva available earlier in the course of lung cancer treatment, offering a non-chemotherapy choice for all NSCLC patients in the maintenance setting."

The sNDA filing is based on a pivotal Phase III placebo-controlled, randomized, double-blind trial known as SATURN. On May 14, 2009, OSI announced data from the SATURN study, which was formally presented at the 45th Annual Meeting of the American Society of Clinical Oncology on May 31, 2009 in Orlando, Fla.

About SATURN

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 (150 mg) or placebo if their cancer did not progress. The primary endpoint of the study was progression-free survival in the overall population, as determined by investigators, and 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 study met both of its co-primary endpoints by demonstrating a statistically significant 41% improvement in the time patients live without their disease worsening (as measured by progression free survival, or PFS) compared with placebo (Hazard Ratio = 0.71, p-value <0.00001; pfs =" 0.69," hr="0.76," value="0.0148," n="359);" hr="0.68," n="525).">

Pre-planned biomarker analyses of tissue samples collected as part of the SATURN protocol provided important information on the potential role of EGFR mutations and K-ras mutations in predicting possible outcomes of Tarceva therapy in NSCLC patients. The subgroup analysis of patients whose tumors possessed an activating EGFR mutation and were eligible for analysis (n=49) demonstrated a statistically significant ten-fold increase in the time patients live without their disease worsening (as measured by PFS) for patients treated with Tarceva compared with placebo. The hazard ratio was 0.10 (p-value <0.0001). hr="0.78," n="388).">

There were no new or unexpected safety signals observed in the SATURN study. Adverse events were consistent with those observed in previous Tarceva studies in NSCLC, and included rash (49.2% with Tarceva versus 5.8% with placebo) and diarrhea (20.3% with Tarceva versus 4.5% with placebo). Dose reductions were necessary in 11% of the patients treated with Tarceva versus 1% of those treated with placebo. Discontinuations due to adverse events were necessary for 4.6% of the patients in the Tarceva arm versus 1.6% in the placebo arm.

About Lung Cancer

According to the American Cancer Society (ACS), lung cancer is the single largest cause of cancer death among men and women in the U.S. and nearly 159,390 Americans are expected to die from the disease in 2009. Most people with lung cancer are diagnosed with advanced stage disease that cannot be surgically removed or has spread to other parts of the body. The majority of people with advanced lung cancer survive less than one year. NSCLC is the most common type of lung cancer.

About Tarceva

Tarceva is a once-a-day pill that targets the EGFR pathway. Tarceva is designed to inhibit the tyrosine kinase activity of the EGFR signaling pathway inside the cell, one of the critical growth factors in NSCLC and pancreatic cancers. 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. Results from two multicenter, placebo-controlled, randomized Phase III trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of Tarceva with platinum-based chemotherapy (carboplatin and paclitaxel or gemcitabine and cisplatin) and its use is not recommended in that setting. In pancreatic cancer, Tarceva is indicated in combination with gemcitabine 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.

Tarceva Safety

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 (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); 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 heart attack 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 non-small cell lung cancer 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 : www.medicalnewstoday.com

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