Fund, trial, treat

Tuesday, April 13, 2010

Professor Françoise Meunier, Director General of the European Organisation for Research and Treatment of Cancer, advocates the need for more academic research in the area

Every year, 3.2 million European citizens are diagnosed with cancer. Overall, the five-year survival is still 50%, leaving a great need for major improvement. Clinical cancer research is paramount for advancing medical science and ensuring rapid application of discoveries arising from fundamental sciences research activities.

Why European IDCT are needed
Investigator-Driven Clinical Trials (IDCT) are independent from the industry, guaranteeing an objective evaluation and establishing optimal therapeutic strategies on a multidisciplinary base. Such clinical studies are crucial for patients, investigators, and for society, and this includes the authorities in charge of healthcare expenses. In fact, such clinical research provides the evidence needed for establishing treatment recommendations and ultimately guaranteeing the proper use of public healthcare resources.

IDCT are warranted for the validation of new treatment strategies that involve the combination of several drugs, but also different treatment modalities such as surgery, radiotherapy, chemotherapy, immunotherapy, cells therapy, etc., in a multidisciplinary setting.

IDCT are sometimes the only way to investigate treatment for rare cancers not attracting pharma industry's interest, or specific populations representing methodological challenges that can be best addressed by academic researchers, like clinical trials in the elderly cancer patient population. The proportion of the European population aged 65 years and older is projected to increase sharply in the coming decades. About 60% of all cancers occur over the age of 65. Decline in organ function and comorbidities are additional risk factors for the treatment of elderly patients with cancer. Some elderly patients cannot tolerate aggressive and intensive therapy. Optimal treatment strategies need to be developed in order to meet elderly population needs.

New techniques, new challenges
There is increasing interest and excitement in new biological response modifiers for cancer therapy. Clinical trials now need to take into account advancements in the understanding of cancer biology, new treatment modalities, and continuing progress in imaging technologies. Subtle changes in cancer density or margins could signal a useful response status at an early stage in therapy. Other features, such as blood flow, might also become important response measures in the future, and metabolic changes could yield additional information. Using traditional methodologies, assessment of tumour response is in the order of weeks or months, but newer imaging technologies such as PET and MRI can reduce this time to days or even hours. The ability to gain a better understanding of the three dimensional anatomical and pathological structure of cancers is a major advantage of imaging-based evaluation of response to cancer therapy.

Today the heterogeneity amongst the way images are collected (different time points, variable quality, and cameras from different manufacturers) hampers their full use in clinical research. Imaging data needs to be part of the clinical trial database, just like any other information collected during the trial. This is the reason why the EORTC took the decision in 2008 to develop an imaging platform. The EORTC Imaging Platform has been set up to allow exchange, central storage, and remote review of images coming from patients treated in their clinical trials. This platform is supported by the international community of experts composed of radiologists, nuclear physicians and clinician, and members of the EORTC Imaging Group. Standardised procedures are being developed for functional image quality assured acquisition and reconstruction.

Ultimately, the integration of high quality imaging will improve the clinical trials quality and optimise the identification of the active anticancer agent in order to deliver the appropriate treatments to cancer patients who are most likely to benefit. Better quality trials will allow early stopping of the development of inactive investigational products and avoid unnecessary burden to the patients and waste of resources.

As an example of the successful implementation of advanced imaging in an international clinical trial: the H10 EORTC/GELA randomised Intergroup trial (EORTC 2005¹) on early FDG-PET scan guided treatment adaptation versus standard combined modality treatment in 1,600 patients with supradiaphragmatic stage I/II Hodgkin's lymphoma. The treatment is stratified according to pre-treatment risk profile and guided according to early FDG-PET scan evaluation. This response-adapted strategy is expected to result in continued high efficacy but reduced toxicity. So far, 1,327 patients have already entered the study.

Why IDCT need support
Independent clinical research is not a luxury. The public health values of IDCT need to be recognised. A dynamic European clinical research area is the only way to promote patients access to state-of-the-art treatments.

Promoting high-quality independent academic clinical research in Europe does not mean the absence of collaboration with industry. Indeed, it is important to promote a new model of collaboration with industry and effective partnerships, including for registration trials, but preserving the independence of the academic community. But after registration of a compound, there are still numerous questions to be answered before setting optimal therapeutic strategies.

However, running a pan-European clinical trial has become a real challenge given the lack of harmonisation of the European legislative framework and the sometimes divergent outcomes from ethics committees' reviews of a study protocol, the divergent insurance requirements for the sponsor, and the extra costs for the hospital related to the treatment of patients participating in clinical trials.

Clinical research is a high resource-consuming activity and IDCT sponsors do not have financial resources comparable to those of the pharmaceutical industry. The independence of academic sponsors and their capacities to conduct high quality studies on treatment strategies must be preserved.

How to support IDCT in Europe
It is widely accepted that the research in Europe is heavily fragmented and duplicated amongst member states. Funding available for international research is scarce since about 85% of the funding is available only at national level.

Efficient targeted and individualised treatment will be developed only through large international trials involving strong translational research components using advanced techniques, eg. functional imaging, and recruiting a sufficient number of patients with rare tumours as well as common tumours, as there is a need to evaluate subgroups of patients with selected molecular markers and genetic expressions. Too much public money is spent on research on the national base only, and not leading to relevant and convincing international studies readily applicable throughout Europe.

Cancer clinical research needs to be performed on a pan-European scale since the resources, in term of patients and clinical expertise, are generally not available on a national base. The coordination and cooperation between national research programmes should be encouraged. Increasing the availability of funding for high standard international clinical research is fundamental for improving cancer patients' access to innovative medicines, and therefore increasing the chances for cancer patients to live longer and with a better quality of life.

The duplication of efforts should be avoided and sufficiently powered clinical trial should be privileged. The European Commission Research Framework Programmes do not offer sufficient funding opportunities for large international clinical trials. Therefore, we recommend the creation of the equivalent of the successful European Research Council at European level, eg. European IDCT Fund, with the mission to fund a significant number of international academic clinical trials in all disease areas every year through a competitive process targeting scientific excellence and public health added value.

The European Parliament in its resolution of 10th April 2008 on combating cancer in the enlarged EU1 stresses the importance of prevention, diagnosis and treatment, as well as cancer related research to reduce the burden of cancer in Europe and calls the European Commission, Council and member states to take appropriate actions. With the European Partnership for Action Against Cancer proposed by the European Commission, we hope that funding for a significant number of European high-quality IDCT will become a reality.

1 European Parliament Resolution of 10th April 2008 on Combating Cancer in the Enlarged European Union, B6-0132/2008 / P6-TA-PROV (2008)0121, available at: www.europarl.europa.eu/sides/getDoc.do?type=TA&reference=P6-TA-2008-0121&language=EN