With the recent FDA approvals of pembrolizumab and nivolumab, and a host of additional immunomodulatory agents entering clinical development each year, the field of cancer immunotherapy is changing rapidly. Strategies that can assist researchers in choosing the most promising drugs and drug combinations to move forward through clinical development are badly needed in order to reduce the likelihood of late-stage clinical trial failures. On October 5, 2014, the Cancer Immunotherapy Consortium of the Cancer Research Institute, a collaborative think tank composed of stakeholders from academia, industry, regulatory agencies, and patient interest groups, met to discuss strategies for de-risking immunotherapy development, with a focus on integrating preclinical and clinical studies, and conducting smarter early-phase trials, particularly for combination therapies. Several recommendations were made, including making better use of clinical data to inform preclinical research, obtaining adequate tissues for biomarker studies, and choosing appropriate clinical trial endpoints to identify promising drug candidates and combinations in nonrandomized early-phase trials.Cancer Immunol Res; 4(4); 279-88. ©2016 AACR (Free AACR Whitepaper).
©2016 American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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CXCR4 is a G protein-coupled receptor with excellent potential as a therapeutic target for a range of clinical conditions including stem cell mobilization, cancer prognosis and treatment, fibrosis therapy and HIV. We report here the development of a fully human single-domain antibody-like scaffold termed an i-body, the engineering of which produces an i-body library possessing a long complementarity determining region (CDR) binding loop, and the isolation and characterisation of a panel of i-bodies with activity against human CXCR4. The CXCR4-specific i-bodies show antagonistic activity in a range of in vitro and in vivo assays including inhibition of HIV infection, cell migration and leukocyte recruitment but, importantly, not mobilization of hematopoietic stem cells. Epitope mapping of three CXCR4 i-bodies AM3-114, AM4-272 and AM3-523 revealed binding deep in the binding pocket of the receptor.
Copyright © 2016, The American Society for Biochemistry and Molecular Biology.

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SUMMARYHistone posttranslational modifications represent a versatile set of epigenetic marks involved not only in dynamic cellular processes, such as transcription and DNA repair, but also in the stable maintenance of repressive chromatin. In this article, we review many of the key and newly identified histone modifications known to be deregulated in cancer and how this impacts function. The latter part of the article addresses the challenges and current status of the epigenetic drug development process as it applies to cancer therapeutics.
Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

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Patient-reported outcome (PRO) data are increasingly being implemented in oncology clinical trial research to evaluate treatment benefit, such as disease-related symptoms, treatment-related adverse events, and health-related quality of life impacts. However, only a small amount of PRO data collected is used to support labeling claims, leaving a substantial amount of data that could be shared by sponsors to further convey treatment benefit from the patient perspective.
This paper describes how pharmaceutical sponsors can realize the value of PRO data derived from oncology trials with regard to the following stakeholders: payers, health care providers (HCPs), and patient advocacy groups. Further, ideas are presented for integrating PRO data and implementing PRO assessments within oncology, by stakeholder type. Finally, a summary is provided to describe how PRO data can benefit the patient by facilitating better, more symptom-focused care and enhancing treatment decisions.
With the goal of motivating further use of PRO assessments in oncology, we present examples of how payers utilize PRO data to inform reimbursement decisions (eg, PRO data inform decisions made by Germany׳s Institute for Quality and Efficiency in Health Care and the United Kingdom׳s National Institute for Health and Care Excellence); how communication of results with patient advocacy groups can lead to a better understanding of what is important to patients; and how HCPs can use PRO instruments to inform patient treatment decisions through real-world application.
Integrating PRO data can enhance health care by allowing the patient’s voice to carry beyond regulatory decisions and into those made by payers and HCPs, which are crucial to quality care and assessing the value of care. Utilizing PRO assessments and communicating results to key stakeholders in the oncology space can allow sponsors to report treatment benefit and, more importantly, can provide valuable insight into the patient treatment experience.
Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

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To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases.
The selection of Drug-Adverse Event pairs was based on public health impact, regulatory relevance, and the possibility to study a broad range of methodological issues. Common protocols and data analytical specifications were jointly developed and independently and blindly executed in different databases in Europe with replications in the same and different databases.
The association between antibiotics and acute liver injury, benzodiazepines and hip fracture, antidepressants and hip fracture, inhaled long-acting beta2-agonists and acute myocardial infarction was consistent in direction across multiple designs, databases and methods to control for confounding. Some variation in magnitude of the associations was observed depending on design, exposure and outcome definitions, but none of the differences were statistically significant. The association between anti-epileptics and suicidality was inconsistent across the UK CPRD, Danish National registries and the French PGRx system. Calcium channel blockers were not associated with the risk of cancer in the UK CPRD, and this was consistent across different classes of calcium channel blockers, cumulative durations of use up to >10 years and different types of cancer.
A network for observational drug effect studies allowing the execution of common protocols in multiple databases was created. Increased consistency of findings across multiple designs and databases in different countries will increase confidence in findings from observational drug research and benefit/risk assessment of medicines. Copyright © 2016 John Wiley & Sons, Ltd.
Copyright © 2016 John Wiley & Sons, Ltd.

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