Innovative treatments and quality radiotherapy are essential
Overall survival from childhood malignancies has dramatically improved, with survival rates reaching over 80%, yet some types of cancer remain a challenge. Professor Gilles Vassal, Institut Gustave Roussy, Villejuif, France, says innovative therapies could effectively target several paediatric malignancies and help save far more young lives than before
Research in paediatric malignancies has been quite successful over the past fifty years, allowing for the average survival rate of children and adolescents with cancer to grow to the current 80% in Europe. However, these major progresses are not equally applied all over the continent, and several problems relating to access of the best possible treatment persist.
Innovative therapies, for instance, could effectively target several paediatric malignancies which are still refractory and, thus, save many young lives. However, while new experimental therapies are targeting adult cancer patient’s immune system and molecular tumour profiling are nowadays becoming widely available in Europe, less than 1 in 10 children in relapse with a not curable cancer has access to innovative medicines today, and investment in new drug development in paediatric oncology is insufficient.
To identify new ways to accelerate new oncology drug development for the paediatric population is one of the priorities of the European Society for Paediatric Oncology (SIOPE), as highlighted in its European Strategic Plan. In this context, and together with the Cancer Drug Development Forum (CDDF) and the European ‘Innovative Therapies for Children with Cancer’ (ITCC) academic consortium, SIOPE created the multi-stakeholder ACCELERATE platform which makes paediatric haemato-oncologists and scientists, parent/patient advocates, pharmaceutical companies and regulatory representatives discuss and formulate possible solutions to this complex and multifaceted problem.
Paediatric drug development is currently regulated in Europe via the EU Regulation on medicinal products for paediatric use 1901/2006. Also known as the ‘Paediatric Regulation’, it came into force in 2007 and aimed to: a) facilitate the development and availability of medicines for children aged 0 to 17 years; b) ensure that medicines for use in children are of high quality, ethically researched and authorised appropriately; and c) improve the availability of information on the use of medicines for children, all this without subjecting children to unnecessary trials or delaying the authorisation of medicines for use in adults. Although this Regulation did change the landscape of drug development before 2007, it didn’t represent a solution for paediatric cancers: too few drugs targeting paediatric oncology are currently under development, and it does not yet address adequately the urgent needs of children and adolescents with cancer.
This piece of legislation allows pharmaceutical companies to derogate to the requirement to initiate a paediatric investigation plan when the target disease or condition is only present in adults and, because of these waivers, several drugs potentially beneficial for a paediatric malignancy were not investigated in children. While the way a specific drug compound works (its “mechanism of action”) in an adult type of cancer may be relevant to a malignant type that only occurs in children, the current system overlooks this potentially life-saving use of a new drug for children. Furthermore, delays in starting paediatric investigation plans and insufficient incentives to pharmaceutical companies represent potential barriers.
Members of the ACCELERATE platform, including the Unite2Cure group of parents, parent organisations and patient advocates who are calling for better access to treatment for children and young people with cancer, decided this year to jointly propose some amendments to the Regulation:
i) Suppress class waivers that are both scientifically and medically unjustified and run paediatric development based on drug mechanism-of-action instead of adult indication;
ii) Set up an efficient system to choose and prioritise the potentially best new oncology drugs to develop in children;
iii) Start early the paediatric development plans well before first marketing authorisation to speed up innovation and reduce off-label use;
iv) Break the 18 years’ dogma;
v) Introduce a more efficient and adapted system of rewards and sanctions.
In May 2016, a few representatives from SIOPE and Unite2Cure had the opportunity to meet the European Commissioner for Health and Food Safety, Vytenis Andriukaitis, and explain the concerns of the paediatric cancer community in this regards.
More recently, the proposals for change in the regulation and its implementation were discussed and warmly welcomed at the conference ‘Review of the EU Paediatric Medicines Regulation – Let’s do more for children with cancer’ (7 September 2016, Brussels). Taking place at the European Parliament, the event was hosted by Elena Gentile MEP (S&D, IT), supported by Glenis Willmott MEP (S&D, UK), and co-organised by the MEPs Against Cancer (MAC) European Parliament Group, Cancer Research UK (CRUK) and SIOPE.
In 2017, the Commission will publish the 10-years report of the regulation and define what is the future. It is crucial that the needs of the paediatric population with cancer are taken into account at a time when therapeutic innovations are dramatically accelerating in adults: children and adolescents should not be left apart.
Assuring quality and excellence in radiotherapy
Another aspect related to equal access to quality care in Europe is that “cure is not enough.” We should always ensure that the quality of the treatment young patients receive will only entail minimal treatment-related side effects on the long term. Reducing the risk of recurrence and long-term toxicity is an essential aspect of care but, still today, the centres delivering multidisciplinary treatments in Europe greatly vary in their capability to meet certain minimum standards of care in the delivery of the therapies and in monitoring patient outcomes.
To assess and improve the effectiveness of the radiotherapy treatments is an important condition to obtain better and more equitable outcomes in children and adolescents with cancer. This is why, thanks to the collaboration between SIOPE and EORTC, the QUARTET project (Quality and Excellence in Radiotherapy and Imaging for Children and Adolescents with Cancer across Europe in Clinical Trials) will investigate and assess the effectiveness of radiotherapy in paediatric cancers through an online prospective quality assurance programme.
Over a period of 5 years and with an estimated number of 500 patients included per year, the project will ensure a centralized review of prospective fields and radiation treatment plans for every child and adolescent before radiotherapy, in order to make necessary amendments if needed. The QUARTET group will cover children and adolescents treated for neuroblastoma, rhabdomyosarcoma and brain tumours as part of 9 European prospective clinical trials. More specifically, the project will use the EORTC radiotherapy quality assurance platform with expert paediatric radiotherapists, as part of the clinical trials implemented within the SIOPE community. QUARTET will also create a database for the real-time use of such quality control data and evaluation and conduct research projects using the data collected. This important project has been funded thanks to the generosity of the Luxembourg foundation ‘Fondatioun Kriibskrank Kanner’.
In conclusion, introducing safer and more innovative treatments into standard care is an essential aspect of ensuring better outcomes for all children and adolescents with cancer. Both these important projects – ACCELERATE and QUARTET – are inscribed in the wider scope of the SIOPE Strategic Plan ‘A European Cancer Plan for Children and Adolescents’, recently endorsed by the European paediatric cancer community.