New Pathways In The Treatment Of Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related mortality in both men and women in the United States and throughout the world. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Sadly, most cases of lung cancer are diagnosed at an advanced stage, conferring a poor prognosis.

Should Phase III results be positive, the next step is filing a New Drug Application, for eventual FDA approval. Occasionally Phase IV trials are run, to evaluate the side effects, risks, and benefits of an already approved drug over a longer period of time, and in a larger number of people than in phase III clinical trials.

Typical first-line therapy (the initial treatment used) for advanced NSCLC patients in the United States is paclitaxel plus carboplatin. There are many possible side effects including nausea, increased risk of infection, anemia, and hair loss. Carboplatin can cause kidney damage, while paclitaxel can cause aching joints and muscles, and lowered blood pressure.

An examination of Phase III clinical trials published from 2001-2008 reveals that the one-year survival rate for patients receiving paclitaxel and carboplatin first-line therapy was on average only about 40%, the weighted average for median survival was 9.7 months, and the objective tumor response (defined as greater than 30% tumor shrinkage) rate was about 27%.

Could the efficacy of these agents be improved, and the side effects lessened? Novelos Therapeutics, Inc., a New England-based biopharmaceutical company [www.novelos.com], certainly thinks so. The company's lead product, NOV-002, is presently in a Phase III clinical trial, with top-line trial results expected later in the first quarter of 2010.

NOV-002 acts in conjunction with paclitaxel plus carboplatin as a chemopotentiator and a chemoprotectant. Thus, NOV-002 makes the chemo more effective, while lessening the side effects. NOV-002 is already approved in Russia, where excellent results have been observed. Related Russian Phase II trials demonstrated that NOV-002 increased the one-year survival of advanced NSCLC patients from 17% to 63%, and improved tolerance of chemotherapy.

Additional studies suggest that NOV-002 efficacy is not limited to particular types of tumors, or chemotherapy agents.

Novelos president and CEO Harry Palmin is enthusiastic. "We are on track for our pivotal Phase III trial to conclude this quarter. "Should this registrational trial be positive, we will proceed with filing a New Drug Application (NDA) in 3Q 2010. Thereafter, based on our Fast Track designation, we would project FDA approval for first-line treatment of advanced NSCLC in combination with chemotherapy in 1Q 2011."

Other promising new approaches in chemotherapy involve attaching the drugs to monoclonal antibodies, which could afford benefits in efficacy and reduction of side effects. These antibodies can be designed to bring the chemo agent directly to the tumor. Similar benefits are said to occur with liposomal therapy, whereby the drugs are packaged inside liposomes (synthetic fat globules).

With annual diagnoses of NSCLC in the United States approaching 200,000 and the annual death toll close to 150,000 any improvements in therapy are surely welcomed, but we still have a long way to go.

Michael D. Shaw
Exec VP
Interscan Corporation

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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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