TheJoint Action on Rare Cancers

Paolo G. Casalipaolo.casali@istitutotumori.mi.it

www.jointactionrarecancers.eu

www.jointactionrarecancers.eu

rare

diseases

cancerrare

cancers

rarecancers

Eur J Cancer 2011;47:2493

1. Pediatric cancers

2. Haematologic rare neoplasms

3. Sarcomas4. Rare thoracic cancers5. Neuroendocrine tumours6. Head & neck cancers7. Central nervous system tumours 8. Rare female genital cancers9. Rare urological and male genital tumours10. Endocrine gland tumours11. Digestive rare cancers12. Rare skin cancers & non-cutaneous melanoma

Rare cancers…

childhood

Rare cancers…

haematologicalchildhood

Rare cancers…

childhoodhaematological

solid of the adult

“Orphan drugs”

“unlikely that marketing would generate sufficient returns to justify the investment needed for development”

EU «Orphan Regulation»

10-year marketing exclusivity fee reductions and exemptions specific scientific advice protocol assistance national incentives EU-funded research

Registration & reimbursementrisk…

p

t

p

t

* in 2017 RCE is also supported by Lilly and AbbVie

17.

Call for increased integration of local, national and European centres of expertise into European reference networks, based on specific criteria as set out in the Commission’s proposed Directive on the application of patients’ rights in cross-border healthcare , in order to provide the necessary sound organisational structures for more efficient clinical research and early transfer of research data into clinical practice, thus improving the clinical management of rare cancers.

“will providehighly specialised healthcare for rare or low prevalence complex diseases or conditions”

promote good quality and safe care to patients by fostering properdiagnosis, treatment, follow-up and management of patientsacross the Network

empower and involve patients offer and promote multi-disciplinary advice for complex cases develop and implement clinical guidelines and cross-border patient

pathways exchange, gather and disseminate knowledge, evidence and

expertise within and outside the Network promote collaborative research within the Network reinforce research and epidemiological surveillance, through

setting up of shared registries exchange and disseminate knowledge and best practices, in

particular by supporting national centres and networks

Objectives

With regard to RCs in the EU, to improve:1. Epidemiological surveillance2. Quality of care through ERNs3. Clinical practice guidelines4. Innovation5. Medical and Patient education6. Health policy measures7. Patient empowerement

Work packages

WP

1 Coordination INT, IT2 Dissemination NKUA, GR3 Evaluation CSF, FI4 Epidemiology INT, IT

5 Assuring Quality of Care OECI

6 Clinical practice guidelines DKG, DE

7 Innovation and access to innovation WIV-ISP, BE

8 Medical education UP, HU

9 Childhood Cancers SIOPE10 Rare Cancer Policy ICO, ES

18 MSs 34 ass. partners

Distance case sharing

Big data & machine learning…

PLoS One 2015;10:e0141357

«Big data» & knowledge generation…

R p<0.05

Milan, 2018

Methodological implications(vs clinical trials!)

Technological windows ofopportunity

Added values for rare cancers

“BIG DATA, AI & RCs”

Martinalbo J et alESMO 2016

Martinalbo J et alESMO 2016

London, June 30th 2016

Adaptive licensing

“a prospectively planned processby which an early authorizationin a restricted patient populationis followed by iterative phasesof evidence-gathering and adaption of the marketing authorization to broader patient populations”

16 April 2018

Oye KA et al. Clin Pharmacol Ther 2016;100:626

The Bayesian probabilityin clinical research…

the probabilitythat a treatment is effective…

The frequentist probabilityin clinical trials…

the probabilityyou had to find this differenceif there were no difference(null effect)…

p<0.05

Mr. Bayes & Mr. Price. Phil Trans 1763;53:370

P[A|B] = P[A] x P[B|A]P[B]

The Bayes theorem…

Mr. Bayes & Mr. Price. Phil Trans 1763;53:370

J Natl Cancer Inst 2011;103:2

Clinical decision-making Methods to combine evidence New study designs Surrogate end points Organization of studies

London, October 3rd 2014

London, April 30th 2015

Pharma

Regulators

Pharma

RegulatorsResearchers

Pharma

RegulatorsResearchersPatients

…….

Frankfurt, 18 April 2017

SARCOMAS

Approval vs reimbursement…

Pandora’s boxJ.W. Waterhouse - 1896

Eur J Cancer 2011;47:2493

Precision oncology…

Precision medicine

paolo.casali@istitutotumori.mi.it

@casali_pg