Personalized Cancer Therapy Requires New Strategies for Cancer Drug Development

Millions of cancer patients worldwide may soon be able to receive more effective, personalized treatments for their disease thanks to developments in the understanding of cancer biology, experts will say at the Cancer Biology for Clinicians Symposium organized by the European Society for Medical Oncology (ESMO) in Nice, France on 26-27 November.

To make the most of this coming transformation, governments, pharmaceutical companies and doctors urgently need to adapt the way drugs are developed, the experts say.

"Cancer therapy is arguably at the most exciting time in its history," said José Baselga, from MGH Cancer Center in Boston, USA, co-chair of the symposium and ESMO Past-President. "It is at the confluence of two new movements, one toward personalized medicine and the other toward the use of new molecularly targeted cancer therapeutics that exploit the tumor's genetic and molecular signature. These movements provide many challenges, but also the opportunity for making paradigm shifts in the way we think of and treat cancer."

Personalized treatment has become increasingly available for cancers over the past decade. This has partly come about as scientists have found that common tumors such as breast cancer are in fact a mixture of several disease types with distinct molecular features. Meanwhile, molecular targeted drugs have also been developed that inhibit particular molecular targets involved in some cancers.

"As our understanding of cancer biology develops further, these kinds of personalized treatments are expected to become available for many more cancer types," said Fabrice André, from Institut Gustave Roussy, France, ESMO spokesperson co-chairing a session at the symposium. "If we want to facilitate the implementation of this kind of personalized medicine, then we urgently need to develop new strategies for cancer drug development."

In particular, it is time to rethink whether the standard model of testing drugs in large phase-III trials is an effective way to bring these targeted cancer drugs to patients, Dr André noted.

"Regulatory processes are becoming increasingly restrictive in providing patient access to potentially innovative new drugs, because even the largest cancer trials generally involve only a small portion of the cancer patient population, and because the drug development process is often more than a decade from the first preclinical study," he added.

This is related to the fact that drug approval usually needs large confirmatory trials that are being done in an unselected population. There is a need for smaller trials done with selected patients to be highly sensitive, a concept that requires the development of molecular selection and relative platforms for doing that.

"It’s clear that we urgently need a new paradigm for drug development, including targeted patient selection for clinical trials, shorter duration of clinical trials and improvement of the cost effectiveness of bringing a new drug to the market."

The ESMO Cancer Biology for Clinicians Symposium, a two-day meeting featuring some of the most eminent researchers in the field, is designed to inform oncologists about the ways cancer biology is changing clinical practice.

"What is most exciting today is the active dialogue between clinicians and laboratory scientists who share an interest in applying the new knowledge of cancer biology to the diagnosis, treatment, and prevention of the disease," said meeting co-chair Mario Dicato, from Centre Hospitalier de Luxembourg.

"In the near future, cancer treatment decisions will be based on biology," said the third meeting co-chair Jean-Charles Soria, ESMO spokesperson from Institut Gustave Roussy, France. "It is therefore vital that medical oncologists have the skills and the knowledge to bring these advances to their patients. The future of oncology will be personalized medicine, and the community needs to discuss how this will be implemented."

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care. The organization is a powerful alliance of more than 6,000 committed oncology professionals from over 100 countries.

For more information:
Cancer Biology for Clinicians Symposium Program Book

This article was first published online at Onco'Zine - The International Cancer Network

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A Fifth of People with Myelodysplastic Syndromes (MDS) Die Prematurely Because the NHS Won't Fund New Life-extending Drugs

The results of a new British survey, launched today by the UK MDS Patient Support Group, shows that almost a fifth (18 percent) of patients suffering from myelodysplastic syndromes (MDS), malfunctions of the bone marrow in producing the correct quantity and quality of blood cells, could have lived for longer if they had been able to access treatments that are currently not approved by NICE, the UK National Institute for Health and Clinical Excellence, for treatment on the NHS (UK National Health Services).

Furthermore, the survey revealed that more than half (56 percent) of hematologists in the United Kingdom surveyed believe that less priority is given to rarer cancers versus other common cancers.

David Hall, Chairman of MDS UK Patient Support Group, comments: "These results are alarming and distressing. Denying any patient access to life-extending, blood cancer drugs is immoral and contradicts the very principles upon which the NHS was founded. These new treatments have been thoroughly tested and their efficacy demonstrated. It is ironic that the perceived constraints to availability in UK seem to be based exclusively on inadequate finance. Inevitably, post code inconsistency in supply reveals some patients with access to new drugs ahead of a NICE decision to license to the NHS. Other local health authorities choose to allow patients to die prematurely."

The MDS UK Patient Support Group calls upon the Department of Health to re-address this inequality by making proven treatments available to all patients whose life span may otherwise be unnecessarily curtailed.

The British survey also revealed that a majority of hematologists (89 percent) surveyed have
faced situations where they have been unable to provide treatments for their cancer patients that could have potentially extended their patients' survival as these treatments were not readily available on the NHS or not yet approved by NICE.

Furthermore, one in ten (12 percent) of blood cancer experts surveyed feel that it would be unwise to tell some of their patients of the new life-extending treatments that are not yet approved by NICE. The main reasons given were budgetary constraints and the risk of upsetting and distressing patients by informing them of treatments they cannot have.

According to Ghulam Mufti, Professor of Haemato-oncology at King's College Hospital, and Chairman of the UK MDS Forum, "These results highlight the concerning gaps in access to treatments that can prolong and improve the lives of patients living with MDS and other blood cancers. Despite significant advances in the treatment of MDS, the majority of patients cannot get access to and in some cases are not even informed about new life-extending drugs until they have been appraised and approved by NICE - a process that can take up to three years from when the drug is first licensed in the UK."

Professor Mufti continued, "Patients with blood cancers require effective treatment to improve their chances of survival. The impact of waiting even a month for treatment can result in a life or death situation."

Some blood cancer treatments featured in the survey, are not yet available on the NHS and are currently going through the NICE review process.

The aim of the survey titled, The Blood Cancer Treatment Access Survey, was to explore attitudes towards treatment options in haematological cancers and patient access to treatments. The survey data was collected via telephone interviews with 100 haematologists (90 from England and Wales and 10 from Scotland). The respondents surveyed were split between consultants and special registrars. The data was collected during 22nd June to 15th July 2009 by Eggington Research Associates Ltd.

For further information:

• Visit MDS UK Patient Support Group
• National Institute for Health and Clinical Excellence (NICE)

Also read:

• Eggington Research Associates Ltd. 2009, 'The Blood Cancer Treatment Access Survey 2009'
• Leukaemia CARE, 2009 Haematology Survey
• Haematological Malignancy Research Network. (Last accessed 28/08/09).

What is the practical impact of quality cancer research?

How does biomedical and clinical research impact daily practice in cancer care? This question has been asked with increasing frequency over the last decade. Results of a study published earlier this year in the British Journal of Cancer, give the answer. The results shows how research in the United Kingdom is helping to deliver significant clinical improvements for cancer patients in the United Kingdom and around the world.

To date, there are 43 oncology guidelines and associated Health Technology Assessments (HTA) published (up to October 2006) in the United Kingdom. Each guideline and associate HTA has a clear evidence base in the form of references, many of which are papers in peer-reviewed journals. Researchers analyzed these guidelines for cancer care from the National Institute of Health and Clinical Excellence (NICE) and the Scottish Medicines Consortium (SMC), and found that papers from UK-based cancer researchers are cited nearly three times more often than would be expected.

These guidelines form the basis of the clinical care given to cancer patients and are devised from an evidence base which includes peer-reviewed research.

In contrast to held idea that the pharmaceutical industry is the biggest sponsor of biomedical research, the study reveals that Cancer Research UK supported over one-third of the clinical trials which were cited as evidence in these guidelines. The number of studies is more than the pharmaceutical industry as a whole, or the UK government. This outcome seems to confirm that altough the private sector will have an important role in identifying and implementing research priorities in cancer research and offer substantial and welcome funding, it does not set the overall research priority end execution. The main reason is that industry by its very nature is partisan and concerned only with commercially viable areas. On the other hand, government agencies, charitable organizations and universities have wider concerns for all cancer research.

Lead author Professor Richard Sullivan, who conducted this study when he was director of clinical programs at Cancer Research UK, and is now at the London School of Economics and the European Cancer Research Managers Foundation, said: "Our study demonstrates the real practical impact of research funding in the UK and shows that cancer research in the UK is punching above its weight.”

International impact
Previous studies have shown a strong sociological tendency for clinical guidelines to focus on domestic research rather than the best international research. The impact of UK research in this study was compared with a standard set by previous studies measuring how far individual countries are expected to deviate from the international standard.

Professor Sullivan continued: "Even taking into account the fact that UK clinical guidelines are inevitably going to be skewed in favor of UK-based research because of the make-up of our healthcare services, we still found that the impact of UK cancer research on clinical practice was disproportionately higher than would be expected - which is a credit to the exceptionally strong research base that we have in this country. We also found indirect evidence that UK cancer research has as impact internationally - particularly in Western Europe."

In numbers
Cancer research conducted in the UK contributes to approximately 6.5 per cent of the world's oncology research output, but almost 20 per cent of cancer research emanating from the UK contributed to the 43 NICE clinical guidelines which were devised before 2006.

The research team analyzed just over 3000 references which were cited across almost 800 research papers over a period of 25 years. The peak years of guideline references were between 1999 and 2001. They looked at the geographical breakdown of the research as well as the type of research conducted and the impact factors of the journals it appeared in. The researchers noted that studies from universities, hospitals and institutes based in Oxford, Cambridge, Edinburgh and Glasgow were the most frequently cited.

Professor Sullivan noted: "This is an interesting finding...[and] this may be because SMC guidelines tend to pay close attention to research coming out of Scotland - but it was still a significant contribution from the two cities."

Kate Law, director of clinical trials at Cancer Research UK, said: "This research highlights the importance of clinical trials carried out in this country and it's great to see that studies funded by Cancer Research UK played a major contribution towards these guidelines. This demonstrates that our research has a significant impact on the clinical management of cancer patients. NICE is seen to be a world leader in the development of quality, evidence based guidelines for cancer care, so it's crucial that the Government and NHS work together to ensure that these guidelines are being uniformly implemented across the country so that all cancer patients can benefit from them."

Although the impact of studies conducted in the United Kingdom is considerable, British researchers in general are concerned about the increased bureaucracy. One researcher noted that patients with cancer are dying because bureaucracy is stifling research. In general, it takes now takes five times longer than in the early 1990s to get a breast or bowel cancer drug into trials.

Professor Sullivan agreed that: "We absolutely agree that research should be carried out in a proper regulatory framework, but because of complex, contradictory, and opaque regulations patients aren’t being protected, they are being failed." The result is a 'culture of fear' in which many now playing it ultra-safe and avoiding sensitive but potentially important areas of research.

Researchers find it incredibly frustrating the added burden of bureaucratic rules slow down the development of new drugs. They agree that this kind of delay is undoubtedly costing lives. They also feel that the added (European) regulations do not provide greater patient safety.

Even though the increase in guidelines may be a concern, most researchers feel that the NICE recommendations are truly based on systematic reviews of the best available evidence. And even when minimal evidence is available, recommendations are based on the opinion of what constitutes good practice.

Also read:
Lewison G, Sullivan, R. The impact of cancer research: how publications influence UK cancer clinical guidelines, British Journal of Cancer (2008) 98, 1944–1950. Click here for the PubMed abstract.