End points PFS vs OS

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    Hi all,

    I know that most of you are depressed from Wednesday announcement, but the sky is not falling as Overall survival (OS) should have been set as end point instead of progression-free survival PSF .

    According to FDA , A clinical trial will usually define or specify a primary endpoint as a measure that will be considered success of the therapy being trialled (e.g., in justifying a marketing approval). The primary endpoint might be a statistically significant improvement in median overall survival (OS). A trial might also define one or more secondary endpoints such as median progression-free survival (PFS) that will be measured and are expected to be met. A trial might also define exploratory endpoints that are less likely to be met.

    Accoridng to SOUTHOZ ,"In standard cancer treatment the whole aim is to shrink tumors. When tumors increase in size this trips the criteria for PFS its counted as a failure. But for immunotherapies like Cvac tumors may look bigger because they are filled with immune cells, so they appear worse. This causes them to trip the PFS criteria but really the person hasnt progressed at all. The cancer is remaining stable."

    .

    According to FDA the following are the pros and cons for OS and PFS

    http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071590.pdf

    Pros for Overall survival

    Universally accepted direct measure of benefit

    Easily measured

    Precisely measured

    Cons of Overall survival

    May involve larger studies

    May be affected by crossover therapy and sequential therapy

    Includes noncancer deaths

    Pros of PFS

    Smaller samples and shorter follow-up necessary compared with survival studies

    Measurement of stable disease included

    Not affected by crossover or subsequent therapies

    Generally based on objective and quantitative assessment

    Cons of PFS

    Not statistically validated as surrogate for survival in all settings

    Not precisely measured; subject to assessment bias particularly in open-label studies

    Definitions vary among studies

    Frequent radiological or other assessments

    Involves balanced timing of assessments among treatment arms

    Overall survival is the gold standard outcome for oncology clinical trials.

    Don't lose hope

    Below is DNDN FDA approval based on overall survival (OS) not PFS

    PROVENGE Significantly Prolongs Survival in Men with Advanced Prostate Cancer in Pivotal Phase 3 IMPACT Study

    Study Meets Primary Endpoint Showing Statistically Significant Improvement in Overall Survival

    First Active Immunotherapy for Cancer to Prolong Survival

    Full Data to be Presented at Plenary Session at Upcoming AUA Annual Meeting

    Company to Host a Conference Call Today at 9:00 AM ET

    SEATTLE, April 14, 2009 - Dendreon Corporation (Nasdaq: DNDN) announced today that the pivotal Phase 3 IMPACT study of PROVENGE (sipuleucel-T) in men with advanced prostate cancer met its primary endpoint of improving overall survival compared to a placebo control. The magnitude of the survival difference observed in the intent to treat population resulted in the study successfully achieving the pre-specified level of statistical significance defined by the study's design. The safety profile of PROVENGE appeared to be consistent with prior trials.

    The 512-patient, multi-center, randomized, double-blind, placebo-controlled IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment) study enrolled men with metastatic androgen-independent prostate cancer was conducted under a Special Protocol Assessment agreement with the U.S. Food and Drug Administration (FDA).

    PROVENGE is Dendreon's investigational product candidate for men with advanced prostate cancer and may represent the first in a new class of active cellular immunotherapies specifically designed to engage the patient's own immune system against cancer.

    Detailed results from the IMPACT study will be presented during a plenary session at the American Urological Association's Annual Meeting in Chicago on Tues., Apr. 28 at 2:20 pm CT.

    "Survival is the gold standard outcome for oncology clinical trials, and overall survival was the primary endpoint of the IMPACT trial. The positive results from this landmark study provide confirmatory evidence demonstrating that treatment with PROVENGE may prolong survival," said Mitchell H. Gold, M.D., president and chief executive officer of Dendreon. "We are immensely grateful to our clinical investigators and the more than 1,000 men with advanced prostate cancer who have participated in our studies over the last decade and whose courage and contribution have significantly advanced the understanding and treatment of prostate cancer and the potential role of cancer immunotherapies."

    "The successful outcome from the Phase 3 IMPACT study provides validation of the long-pursued goal of harnessing the human immune system against a patient's own cancer," continued Dr. Gold.

    Because the data meet the criteria and specifications outlined in its Special Protocol Assessment (SPA) agreement with the FDA, Dendreon intends to file an amendment to its existing Biologic License Application (BLA) in the fourth quarter of this year to gain licensure of PROVENGE.

    Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than one million men in the United States have prostate cancer, with an estimated 186,320 new cases and approximately 28,660 men who were expected to die from the disease in 2008. Currently there are limited treatment options for men with advanced, metastatic prostate cancer

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