Evolution of end points for cancer immunotherapy trials.
نویسنده
چکیده
The effect of cancer immunotherapies is on the immune system and not directly on the tumour. The kinetics of immunotherapy are characterised by a cellular immune response followed by potential changes in tumour burden or patient survival. To adequately investigate immunotherapies in clinical trials, a new development paradigm including reconsideration of established end points addressing this biology is needed. Over the last 7 years, several initiatives across the cancer immunotherapy community were facilitated by the Cancer Research Institute Cancer Immunotherapy Consortium. They systematically evolved an immunotherapy-focused clinical development paradigm and proposed to redefine trial end points. On that basis, analysis of several large datasets generated throughout the immunotherapy community supports three novel end point proposals. First, results from T-cell immune response assays are highly variable and often nonreproducible. Harmonisation of assays can minimise this variability and support the investigation of the cellular immune response as a biomarker and testing it for clinical surrogacy. Secondly, immunotherapy induces novel patterns of the antitumour response not captured by World Health Organisation criteria or Response Evaluation Criteria in Solid Tumours. New immune-related response criteria were defined which more comprehensively capture all response patterns. Thirdly, survival curves in randomised immunotherapy trials can show a delayed separation, which can impact study results. Altered statistical models are needed to describe the hazard ratios as a function of time, and differentiate them before and after separation of curves to improve planning of phase III trials. Taken together, these recommendations may improve our tools for cancer immunotherapy investigations.
منابع مشابه
Assessing oncologic benefit in clinical trials of immunotherapy agents.
BACKGROUND USA Food and Drug Administration approval for cancer therapy requires demonstration of patient benefit as a marker of clinical efficacy. Prolonged survival is the gold standard for demonstration of efficacy, but other end points such as antitumor response, progression-free survival, quality of life, or surrogate end points may be used. DESIGN This study was developed based on discu...
متن کاملایمونوتراپی تومور، تاریخچه و دست آورد ها
Cancer treatment is one of the main fields in basic and clinical research. Immunotherapy or using immune response is considered as one of the most important and effective complementary approaches in cancer therapy after surgery, chemotherapy and radiotherapy. In recent years many clinical trials have investigated this approach. The complications involved in immune response against a tumor calls...
متن کاملDendritic Cells and Their Role in Cancer Immunotherapy
Dendritic cells (DCs) are antigen presenting cells with unique capability to take up and process antigens in the peripheral blood and tissues. They subsequently migrate to draining lymph nodes where they present these antigens and stimulate naive T lympho-cytes. During their life cycle, DCs go through two maturation stages and are referred to as immature and mature cells, respectively. While im...
متن کاملWhole Tumor Cell Vaccine Adjuvants: Comparing IL-12 to IL-2 and IL-15
Cancer immunotherapy (passive or active) involves treatments which promote the ability of the immune system to fight tumor cells. Several types of immunotherapeutic agents, such as monoclonal antibodies, immune checkpoint inhibitors, non-specific immunomodulatory agents, and cancer vaccines are currently under intensive investigation in preclinical and clinical trials. Cancer vaccines induce pe...
متن کاملA clinical development paradigm for cancer vaccines and related biologics.
Therapeutic cancer vaccines are a heterogeneous group of complex biologics with distinctly different clinical characteristics than cytotoxic agents. The current clinical development paradigm used for oncology drug development is based on criteria developed for cytotoxic agents. More flexible and focused developmental guidelines are needed to address the unique characteristics of therapeutic can...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Annals of oncology : official journal of the European Society for Medical Oncology
دوره 23 Suppl 8 شماره
صفحات -
تاریخ انتشار 2012