Publications by authors named "Patricia Blanc"

12 Publications

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ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients.

Eur J Cancer 2020 03 24;127:52-66. Epub 2020 Jan 24.

BMS, USA.

The third multistakeholder Paediatric Strategy Forum organised by ACCELERATE and the European Medicines Agency focused on immune checkpoint inhibitors for use in combination therapy in children and adolescents. As immune checkpoint inhibitors, both as monotherapy and in combinations have shown impressive success in some adult malignancies and early phase trials in children of single agent checkpoint inhibitors have now been completed, it seemed an appropriate time to consider opportunities for paediatric studies of checkpoint inhibitors used in combination. Among paediatric patients, early clinical studies of checkpoint inhibitors used as monotherapy have demonstrated a high rate of activity, including complete responses, in Hodgkin lymphoma and hypermutant paediatric tumours. Activity has been very limited, however, in more common malignancies of childhood and adolescence. Furthermore, apart from tumour mutational burden, no other predictive biomarker for monotherapy activity in paediatric tumours has been identified. Based on these observations, there is collective agreement that there is no scientific rationale for children to be enrolled in new monotherapy trials of additional checkpoint inhibitors with the same mechanism of action of agents already studied (e.g. anti-PD1, anti-PDL1 anti-CTLA-4) unless additional scientific knowledge supporting a different approach becomes available. This shared perspective, based on scientific evidence and supported by paediatric oncology cooperative groups, should inform companies on whether a paediatric development plan is justified. This could then be proposed to regulators through the available regulatory tools. Generally, an academic-industry consensus on the scientific merits of a proposal before submission of a paediatric investigational plan would be of great benefit to determine which studies have the highest probability of generating new insights. There is already a rationale for the evaluation of combinations of checkpoint inhibitors with other agents in paediatric Hodgkin lymphoma and hypermutated tumours in view of the activity shown as single agents. In paediatric tumours where no single agent activity has been observed in multiple clinical trials of anti-PD1, anti-PDL1 and anti-CTLA-4 agents as monotherapy, combinations of checkpoint inhibitors with other treatment modalities should be explored when a scientific rationale indicates that they could be efficacious in paediatric cancers and not because these combinations are being evaluated in adults. Immunotherapy in the form of engineered proteins (e.g. monoclonal antibodies and T cell engaging agents) and cellular products (e.g. CAR T cells) has great therapeutic potential for benefit in paediatric cancer. The major challenge for developing checkpoint inhibitors for paediatric cancers is the lack of neoantigens (based on mutations) and corresponding antigen-specific T cells. Progress critically depends on understanding the immune macroenvironment and microenvironment and the ability of the adaptive immune system to recognise paediatric cancers in the absence of high neoantigen burden. Future clinical studies of checkpoint inhibitors in children need to build upon strong biological hypotheses that take into account the distinctive immunobiology of childhood cancers in comparison to that of checkpoint inhibitor responsive adult cancers.
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http://dx.doi.org/10.1016/j.ejca.2019.12.029DOI Listing
March 2020

A European paediatric cancer mission: aspiration or reality?

Lancet Oncol 2019 09;20(9):1200-1202

Department of Pediatrics and Adolescent Medicine, Rigshospitalet University Hospital, and Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1016/S1470-2045(19)30487-5DOI Listing
September 2019

10-year report on the European Paediatric Regulation and its impact on new drugs for children's cancers.

Lancet Oncol 2018 03;19(3):285-287

Innovative Therapy for Children with Cancer, Europe; SIOPE Brussels, Belgium; Department of Clinical Research, Gustave Roussy, Paris-Saclay University, Villejuif, France.

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http://dx.doi.org/10.1016/S1470-2045(18)30105-0DOI Listing
March 2018

Orphan Drug Regulation: A missed opportunity for children and adolescents with cancer.

Eur J Cancer 2017 10 4;84:149-158. Epub 2017 Sep 4.

Innovative Therapy for Children with Cancer, Villejuif, France; Paediatric Drug Development, Children and Young People's Unit, The Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, UK; Division of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research, Sutton, SM2 5NG, UK.

Background: Oncology represents a major sector in the field of orphan drug development in Europe. The objective was to evaluate whether children and adolescents with cancer benefited from the Orphan Drug Regulation.

Methods: Data on orphan drug designations (ODDs) and registered orphan drugs from 8th August 2000 to 10th September 2016 were collected from the Community Register of medicinal products for human use. Assessment history, product information and existence of paediatric investigation plans were searched and retrieved from the European Medicine Agency website.

Results: Over 16 years, 272 of 657 oncology ODDs (41%) concerned a malignant condition occurring both in adults and children. The five most common were acute myeloid leukaemia, high-grade glioma, acute lymphoblastic leukaemia, graft-versus-host disease and soft-tissue sarcomas. 74% of 31 marketing authorisations (MAs) for an indication both in adults and children (26 medicines) had no information for paediatric use in their Summary of Product Characteristics (SmPC) at the time of the first MA. Furthermore, 68% still have no paediatric information in their most recently updated SmPC, at a median of 7 years after. Only 15 ODDs (2%) pertained to a malignancy occurring specifically in children and only two drugs received an MA: Unituxin for high-risk neuroblastoma and Votubia for sub-ependymal giant-cell astrocytoma.

Conclusion: The Orphan Drug Regulation failed to promote the development of innovative therapies for malignancies occurring in children. Major delays and waivers occurred through the application of the Paediatric Medicines Regulation. The European regulatory environment needs to be improved to accelerate innovation for children and adolescents dying of cancer.
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http://dx.doi.org/10.1016/j.ejca.2017.07.021DOI Listing
October 2017

[How and what conditions for new drugs in pediatric cancer?]

Rev Prat 2016 01;66(1):16-18

Pédiatre oncologue, département d'oncologie pédiatrique, adolescents, jeunes adultes (DOPAJA), et directeur délégué de la recherche, ensemble hospitalier de l'institut Curie ; professeur de pédiatrie, faculté de médecine Paris-Descartes, Paris, France.

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January 2016

Will the revised class waiver list make it?

Lancet Oncol 2015 Sep;16(9):e425-e426

Institute for Cancer Research, London, UK; European Consortium for Innovative Therapies for Children with Cancer, Villejuif, France.

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http://dx.doi.org/10.1016/S1470-2045(15)00233-8DOI Listing
September 2015

Creating a unique, multi-stakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer.

Eur J Cancer 2015 Jan 27;51(2):218-24. Epub 2014 Nov 27.

Medizinische Universität Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address:

Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders - academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory pressure to propose early Paediatric Investigation Plans (PIPs), missed opportunities to explore new drugs potentially relevant for paediatric malignancies, lack of innovative trial designs and no new incentives to develop drugs against specific paediatric targets are some unmet needs. Better access to new anti-cancer drugs for paediatric clinical studies and improved collaboration between stakeholders are essential. The Cancer Drug Development Forum (CDDF), previously Biotherapy Development Association (BDA), with Innovative Therapy for Children with Cancer Consortium (ITCC), European Society for Paediatric Oncology (SIOPE) and European Network for Cancer Research in Children and Adolescents (ENCCA) has created a unique Paediatric Oncology Platform, involving multiple stakeholders and the European Union (EU) Commission, with an urgent remit to improve paediatric oncology drug development. The Paediatric Oncology Platform proposes to recommend immediate changes in the implementation of the Regulation and set the framework for its 2017 revision; initiatives to incentivise drug development against specific paediatric oncology targets, and repositioning of drugs not developed in adults. Underpinning these changes is a strategy for mechanism of action and biology driven selection and prioritisation of potential paediatric indications rather than the current process based on adult cancer indications. Pre-competitive research and drug prioritisation, early portfolio evaluation, cross-industry cooperation and multi-compound/sponsor trials are being explored, from which guidance for innovative trial designs will be provided.
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http://dx.doi.org/10.1016/j.ejca.2014.10.029DOI Listing
January 2015

Need for change in implementation of paediatric regulation.

Lancet Oncol 2013 Nov;14(12):1156-7

Institut Gustave Roussy, Villejuif, France. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(13)70467-4DOI Listing
November 2013

New drugs for children and adolescents with cancer: the need for novel development pathways.

Lancet Oncol 2013 Mar 20;14(3):e117-24. Epub 2013 Feb 20.

Division of Clinical Research, Institut Gustave Roussy, Paris-Sud University, Paris, France. Electronic address:

Despite major progress in the past 40 years, 20% of children with cancer die from the disease, and 40% of survivors have late adverse effects. Innovative, safe, and effective medicines are needed. Although regulatory initiatives in the past 15 years in the USA and Europe have been introduced, new drug development for children with cancer is insufficient. Children and families face major inequity between countries in terms of access to innovative drugs in development. Hurdles and bottlenecks are well known-eg, small numbers of patients, the complexity of developing targeted agents and their biomarkers for selected patients, limitations of US and EU regulations for paediatric medicines, insufficient return on investment, and the global economic crisis facing drug companies. New drug development pathways could efficiently address the challenges with innovative methods and trial designs, investment in biology and preclinical research, new models of partnership and funding including public-private partnerships and precompetitive research consortia, improved regulatory requirements, initiatives and incentives that better address these needs, and increased collaboration between paediatric oncology cooperative groups worldwide. Increased cooperation between all stakeholders-academia, parents' organisations and advocacy groups, regulatory bodies, pharmaceutical companies, philanthropic organisations, and government-will be essential.
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http://dx.doi.org/10.1016/S1470-2045(13)70013-5DOI Listing
March 2013

[Does the care for the fear of falling bring a profit to community living elderly people who had experienced falls?].

Psychol Neuropsychiatr Vieil 2007 Sep;5(3):225-34

CHU de Saint-Etienne, Hôpital Charité, Gérontologie Clinique, 42055, Saint-Etienne Cedex 2, France.

Introduction: fall is common in old people and has multiple consequences, physical but also psychological, with a fear of falling which results in reduction in the activities of everyday life, loss of autonomy and entry in dependence. The aim of the study was to evluate the benefit of taking into account the fear of falling in the care of old people who had experienced falls.

Methodology: old people who experienced falls and with a good cognitive status were followed in a day hospital during one year. Evaluation including a specific assessment of the responsibility of the psychological factor, the photolangage, was performed before and after multi-field rehabilitation. We used the rating scales ADL, IADL, SF-36, SAFE, and verbal and analogical scales of the fear of falling.

Results: fifteen patients were included (mean age 85 years +/- 5,7). The majority were women living alone, with a good nutritional status, a moderated renal insufficiency, and a comorbidity involving polymedication. Scores on the ADL and IADL scales showed a consolidation of the patients' autonomy, with a slight but significant improvement of the IADL scores (p < 0,05). All scales assessing the fear of falling (visual analogical, verbal scales, SAFE) showed a statistically significant improvement (p<0,001). SF-36 scale, exploring the quality of life perceived by the patients, showed a great deterioration immediately after falling, and a statistically significant improvement on seven of the eight subscales after rehabilitation. The global physical score (GCV) was improved in a nonsignificant way, whereas the global psychic score (MCS) progressed in a statistically significant way (p < 0,001).

Conclusion: this pilot study shows that multi-field rehabilitation and adapted assumption of responsibility of fear of falling brings a benefit in term of quality of life and preservation of autonomy in old people living in the community who had experienced falls.
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September 2007

[Individualization of the frail elderly people and use of health care services].

Psychol Neuropsychiatr Vieil 2003 Sep;1(3):187-96

CHU de Saint-Etienne, Hôpital Charité, Gérontologie clinique.

The challenge of identifying frail elderly subjects is important to optimize the management of care for the old patients. The recognition of frailty allows clinicians to detect subjects whose autonomy is precarious in relation to decreased physical performances and\or vulnerability of their psychosocial stability. A better distinction of healthy old people from frail elderly in an emergency ward makes possible to target the medical care toward the individuals who are more likely to benefit from it and to work out the best strategies of prevention. However, assessment of frailty is time-consuming and there is no consensus on the diagnostic measures. Brief tools to assess the principal components of frailty, which could be included in the routine clinical examination of people over 75 years of age, are currently in progress of validation.
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September 2003

[Should we treat all the diseases of the elderly?].

Therapie 2004 Mar-Apr;59(2):227-32

CHU de Saint-Etienne, Hôpital Charité, Gérontologie Clinique, Saint-Etienne, France.

The coexistence of several diseases, the loss of autonomy and certain social and behavioural factors lead to polymedication. It is important to reduce the number of drugs prescribed to prevent drug-drug interactions or interactions between drugs and a system weakened by age and comorbiditiy. Because of the limited number of therapeutic trials performed in individuals aged >75 years, clinical consideration based on the consensus of experts is the primary way of establishing priorities and making rational choices.
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http://dx.doi.org/10.2515/therapie:2004044DOI Listing
October 2004