ICH research highlights unmet needs of children and young people with cancer and challenges public policy

Despite a global effort to prevent, cure, and control cancer, the specific needs of children and young people have been overlooked, according to academics at the UCL Institute of Child Health (ICH). 

Although 80 per cent of childhood cancers are potentially curable with current treatments, every day roughly 250 children around the world lose their lives to cancer.

What is often seen as the small problem of childhood cancer, is actually a major public health issue, both socially and economically.

A major new Lancet Oncology Series, presents the latest results and ideas from some of the world’s most eminent cancer experts from 19 countries, spanning six continents ‑ highlighting the educational, research, and care needs of children and young people with cancer in all countries, and proposing a broad range of solutions for the next decade.

In particular, they look at how increasingly strict regulatory environments for clinical research are damaging the development of new cancer medicines for children and threatening recent improvements in survival, and outline how the growing threat of childhood cancer in developing nations could be easily managed.

The Series is published to coincide with a special event hosted by Glenis Willmott, Member of the European Parliament (MEP) and EP Rapporteur of the EU Clinical Trials Regulation proposal, in collaboration with the European Society for Paediatric Oncology (SIOP Europe), which will debate these and other issues on childhood cancer at the EU parliament at 3pm [CET] on 20 February 2013.

Remarkable improvements in survival from childhood cancer have taken place in high-income countries over the past 50 years, but further progress is being threatened by increasingly strict research regulations and insufficient development of new drugs, according to a major new Lancet Oncology Series on improving cancer care for children and young people.

“In high-income countries, we have nearly reached optimisation of present anticancer treatments”, says Series leader Professor Kathy Pritchard-Jones from the ICH. “New regulatory approval and research strategies are urgently needed to speed the development of new, effective, and safer treatments for children with cancer, if we are to continue to improve the cure rate, reduce toxicity compared to existing treatments, and minimise side effects in later life.”
Although more children and young people in high-income countries are surviving cancer than ever before, cancer remains the leading cause of death from disease in children aged 1 to 15 years, and more than 5,000 children still lose their lives to cancer every year.

Increased participation in international, collaborative clinical trials has successfully raised survival from 30 per cent to 80 per cent over the last half century. “But an increasingly complex and strict regulatory environment for clinical research and data sharing is limiting children’s access to early-phase clinical trials and delaying the development of new drugs”, explains co-leader Professor Richard Sullivan from the Institute of Cancer Policy, King’s College London. “For example, the implementation of the EU Clinical Trials Directive, in 2004, has almost quadrupled costs, led to substantial delays, and even the discontinuation of trials.”

Other factors leading to longer clinical development include the complex nature of the biology underlying childhood cancers, the difficulty of identifying targets suitable for drug treatment, a lack of long-term sustainable funding for research and development, particularly outside the USA, and little economic incentive for pharmaceutical companies to develop anticancer drugs adapted for children.

To fast-track the most relevant and new medicines for childhood cancers will require a renewed focus on the potential role of adult cancer drugs in children, as well as newer methods and clinical trial design that aim to more rapidly predict the optimal (ie effective and safe) dose.

In recent years, it has been industry that has driven the clinical trials in children to meet regulatory requirements rather than the paediatric oncology expert community who understand the clinical unmet needs of children and young people with cancer, write the authors: “The trend in the past few years for industry to drive the development of clinical research plans contrasts with the need for broad research and development partnerships that can deal with complex biology and drug development.”

“Fostering open collaborations with many groups from industry, regulatory bodies, academia, governments, and patient advocacy will be crucial to speeding up drug development”, says co-author Professor Gilles Vassal from the Institut Gustave Roussy, Paris-Sud University, France. “The key is precompetitive collaboration that benefits all stakeholders, ensuring broad access to the results.”

According to Professor Pritchard-Jones, “new biology-driven approaches are needed, but this will only be achieved through increased international cooperation in clinical trials and sharing of research tissue samples and data. This is necessary as these diseases are already rare, and dividing patients into increasingly smaller biological subgroups might amount to just a handful of trial participants a year in each country.”

She adds: “The introduction of drugs that are less toxic and more targeted than those currently used necessitates a partnership between clinical and translational researchers, the pharmaceutical industry, drug regulators, and patients and their families. This therapeutic alliance will ensure that efforts are focused on the unmet clinical needs of young people with cancer.”

As well as drug development challenges, more needs to be done to address the long-term consequences of cancer treatment. Estimates suggest that one in 1,000 adults in high-income countries are survivors of childhood cancer, and 40 per cent of these survivors experience adverse effects throughout life.

“These are serious issues that can have a real impact on a person’s quality of life”, says Sullivan. “It is essential that academic programmes and trial investigators ensure better follow-up of survivors to appropriately address the complications childhood cancer survivors may experience in later life.”

The authors conclude by calling on every country to develop a national cancer plan that recognises the unique demographic and care needs of young people with cancer, adding that: “If policy makers continue to fail to pay attention to this issue then in 10 years…the infrastructure will not be in place to deal with what will have become the most common disease-related cause of death in childhood.”

Across the developing world, childhood cancer is on the rise, and mortality is high. Once thought of as a rich world disease, cancer is a growing health threat across low-income and middle-income countries (LMCs). A major new Lancet Oncology Series by some of the world’s most eminent cancer experts outlines the biggest challenges to treating childhood cancer in developing nations and proposes strategies to improve care for children and young people.

According to recent WHO estimates, cancer claims the lives of around 100,000 children before the age of 15 every year worldwide. Ninety-four per cent of these deaths occur in low-income countries. Developing countries are already home to nearly 90 per cent of the world’s children and this proportion continues to rise.

“The stark reality is that access to treatment is very poor in LMCs. An unknown proportion of children with potentially curable cancers never receive treatment—not even palliative treatment—and most of those who do receive some form of treatment still die”, says Professor Ian Magrath from the International Network for Cancer Treatment and Research, Belgium, one of the lead authors.

In many LMCs, a lack of awareness about cancer and poor availability of basic healthcare means that children often present with late-stage disease. Doctors in developing countries are often not well trained in cancer diagnosis and may only see a handful of childhood cancers during their entire careers. Moreover, treatment is often poor or non-existent, or too costly for patients to afford. In Africa, for instance, the proportion of cancers that occur in children is roughly 12 times higher than in Europe, but 80 per cent of people in Africa have no access to radiotherapy, cancer surgery, or the infrastructure needed to deliver basic cancer care.

According to Series leader Professor Kathy Pritchard-Jones from the Institute of Child Health, University College London, “Some challenges seen around the world…are not entirely dictated by income or spend on health care, but also by the motivation of politicians to create and develop sustainable infrastructure that recognises the specific needs of children with cancer.” In Mexico, for example, children’s abandonment of cancer treatment has been reduced from 35 per cent to 4 per cent by a combination of the introduction of insurance for the most socioeconomically deprived families (50 per cent of the population), the development of standard treatment protocols, and the accreditation of 49 programmes for childhood cancer.

Investment in health-care systems and capacity (including equipment and drugs), more and better-trained health professionals, and the establishment of regional hospital networks and international collaboration are essential to improving outcomes. In particular, twinning programmes between developed and developing countries, and different regions, can provide international mentoring, medical education, access to up-to-date treatments, and increase participation in international clinical trials.

Additionally, cancer registries (often the only unbiased source of information on cancer burden) are urgently needed to assess the situation within each country and support decision making. In Africa, for instance, only 1 per cent of the population is covered by population-based cancer registries providing data on cancer incidence, compared to more than 80 per cent in North America and Oceania, and 33 per cent in Europe.

“Measurable 5-year survival outcomes, even if substantially less than those of high income countries at first, will help to create a dynamic that is not easily ignored by politicians”, say the authors.

Finally, they add, strategies to dispel the myth that developing countries cannot afford to treat children with cancer are needed. “Because children have their entire lives ahead of them, saving the lives of children has a much greater effect on economic development than does cancer care for older people”, explains Magrath, “Treatment of curable childhood cancers is highly cost effective, even if it is only possible in a few institutions.”