Overall survival: Still the gold standard: Why overall survival remains the definitive end point in cancer clinical trials
Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. The Cancer Journal
(Impact Factor: 4.24).
09/2009; 15(5):401-5. DOI: 10.1097/PPO.0b013e3181bdc2e0
Overall survival (OS) is the gold standard primary end point to evaluate the outcome of any drug, biologic, intervention, or procedure that is assessed in oncologic clinical trials. OS is universally recognized as being unambiguous, unbiased, with a defined end point of paramount clinical relevance, and positive results provide confirmatory evidence that a given treatment extends the life of a patient. Clinical trialists relentlessly attempt to devise more easily measured, cost-effective, and readily available event-driven end points as predictive surrogates of a definitive outcome, such as OS, and reduce the time with which clinical trials deliver definitive results. For some treatment modalities used in a limited number of cancer types, certain event-driven surrogates, eg, progression-free survival or time-to-progression may predict OS benefit. Biologic, cell-based, and vaccine-generated treatments are rapidly expanding the oncologist's armamentarium to combat cancers and pose a dilemma in that response may not be reflected by progression-free survival, time-to-progression, or other surrogates? As targeted therapies march forward, will each new therapy require a unique biomarker validated for every disease indication? Moreover, adjuvant treatments have demonstrated efficacy and given the current limited possibility of cure in the metastatic setting, should other end points, eg, quality-of-life, emerge as valid outcomes to demonstrate benefit. Clinical trials must continue to assess OS until biologically plausible measures are developed and emerge as valid early end point surrogates to replace the gold standard.
Available from: Frédéric L.W.V.J. Schaper
- "However, this culminates into a long duration and high costs of clinical trials. Accordingly, if to be of use for both the pharmaceutical industry and the individual patient, 99mTc-HYNIC-Annexin A5 imaging must be able to accurately and reproducibly predict the outcome of phase 3 clinical trials (e.g., DFS and OS) in a short time window [79,80]. Only then, organizational and economic wins are anticipated. "
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ABSTRACT: Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT). Structural changes, if present, become apparent 1-2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99mTc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1-4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome-based medicine, applicable to all cancer patients.
Cancers 05/2013; 5(2):550-68. DOI:10.3390/cancers5020550
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ABSTRACT: Non-small cell lung cancer (NSCLC) stages over IIIb still remain as an intractable disease. Survival rate of NSCLC stages over IIIb could be increased through chemotherapy and radiation, but results are not satisfactory. Oriental medicine herbal formula, HangAm-Dan (HAD) has been developed for anti-tumor purpose and several previous studies have already reported its effects. The aim of this study is to assess HAD's efficacy on prolonging the survival rate of NSCLC stages over IIIb.
We have administered 3 000 mg of HAD daily to patients. The study included 74 first visit patients of East-West Cancer Center (EWCC) from November 2007 to April 2008, diagnosed with inoperable NSCLC stages over IIIb. Among them, 30 patients were in HAD group and 44 patients were in combined group with conventional therapy and HAD. We have observed and analyzed their overall survival.
Of total 74 patients, overall 1 year, 2 year survival rates and the median survival time were 62.1%, 34.9% and 17.0 months (95%CI: 12.9-21.1). NSCLC stage IIIb patients showed higher survival rates than NSCLC stage IV patients (P=0.408). The 1 year, 2 year survival rates and the median survival time of the combined group were 70.5%, 37.9% and 20.0 months (95%CI: 16.4-24.6). In HAD group, the 1 year, 2 year survival rates and the median survival time were 50.0%, 25.7% and 12.0 months (95%CI: 6.6-17.4). The combined therapy group showed higher survival rates than the HAD group (P=0.034). Each groups treated with HAD for more than 4 weeks showed higher survival rates than those treated for less than 4 weeks, but there was no significant difference (P=0.278). In hazard ratio, the combined therapy group showed lower mortality rate than the HAD group with statistical significance (P=0.040).
HAD could prolong the survival rate of inoperable NSCLC stages over IIIb. HAD is more effective when combined with conventional therapy. In the future, more controlled clinical trials with larger sample in multi-centers are needed to reevaluate the efficacy and safety of HAD.
Zhongguo fei ai za zhi = Chinese journal of lung cancer 11/2010; 13(11):1009-15. DOI:10.3779/j.issn.1009-3419.2010.11.03
Available from: Nicholas P Restifo
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ABSTRACT: Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent completion of several large, randomized phase III clinical trials that in some cases have reported an improvement in progression free or overall survival. However, an honest appraisal of their efficacy reveals modest clinical benefit and a frequent requirement for patients with relatively indolent cancers and minimal or no measurable disease. Experience with adoptive cell transfer-based immunotherapies unequivocally establishes that T cells can mediate durable complete responses, even in the setting of advanced metastatic disease. Further, these findings reveal that the successful vaccines of the future must confront: (i) a corrupted tumor microenvironment containing regulatory T cells and aberrantly matured myeloid cells, (ii) a tumor-specific T-cell repertoire that is prone to immunologic exhaustion and senescence, and (iii) highly mutable tumor targets capable of antigen loss and immune evasion. Future progress may come from innovations in the development of selective preparative regimens that eliminate or neutralize suppressive cellular populations, more effective immunologic adjuvants, and further refinement of agents capable of antagonizing immune check-point blockade pathways.
Immunological Reviews 01/2011; 239(1):27-44. DOI:10.1111/j.1600-065X.2010.00979.x · 10.12 Impact Factor
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