Position paper: new insights into the immunobiology and dynamics of tumor–host interactions require adaptations of clinical studies

ABSTRACT

Introduction

Prospective double-blind placebo-controlled randomized clinical trials (RCTs) are considered standard for the proof of the efficacy of oncologic therapies. Molecular methods have provided new insights into tumor biology and led to the development of targeted therapies. Due to the increasing complexity of molecular tumor characteristics and of the individuality of specific anti-tumor immune reactivity, RCTs are unfortunately only of limited use.

Areas covered

The historical methods of drug research and approval and the related practices of reimbursement by statutory and private health insurance companies are being questioned. New, innovative methods for the documentation of evidence in personalized medicine will be addressed. Possible perspectives and new approaches are discussed, in particular with regard to glioblastoma.

Expert opinion

Highly specialized translational oncology groups like the IOZK can contribute to medical progress and quick transfer ‘from bench to bedside.’ Their contribution should be acknowledged and taken into account more strongly in the development of guidelines and the reimbursement of therapy costs. Methodological plurality should be encouraged.

KEYWORDS:

• Cancer immunotherapy
• guidelines
• conflict of interest
• randomized trials
• tumor immunology
• evidence-based medicine
• dendritic Cells
• newcastle Disease Virus

Article highlights

• New insights into tumor biology and ‘OMICS’ technologies have led to the development of personalized therapies that are only effective for a fraction of patients.

• Some immunological approaches aim at the induction of an anti-tumor immune response, the modulation of the pattern of cytokines and of the tumor microenvironment.

• Development of cancer drugs is expensive and time-consuming. Clinical translation of promising technologies is hampered. Spending on oncologic pharmaceuticals keeps rising with minimal clinical advances.

• The primacy of RCTs and the established methodology of phase I toward phase III trials are being challenged.

• The approval of cancer drugs and the development of guidelines are often based on fragile data and can be associated with considerable conflicts of interest.

• Small translational clinics can contribute valuable clinical insights and methodologic innovation.

• The establishment of large databases of results from individual patients and the development of innovative study designs could lower expenditures and enable clinical translation of scientific findings.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A peer reviewer on this paper has served on the advisory boards for Pfizer, BMS, Genentech, EMD Serono, Novartis, Merck, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Amgen, Eisai, Bicycle Therapeutics, has received research support from Boehringer-Ingelheim, Bayer, Pfizer, Merck, Sanofi, Astrazeneca, has received travel bursaries from BMS and Astrazeneca, has received speakers fees from Physicians Education Resource (PER), Onclive, Research to Practice, Clinical Care Options and has served on the steering committee of trials for BMS, Bavarian Nordic, Seattle Genetics, QED (all unpaid), and Astrazeneca and Debiopharm (both paid). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper received no funding.