MPNCEE2018 presentions Friday by MPNE

MPNCEE 2018 presentations Friday, 21st September 2018

www.melanomapatientnetworkeu.org/mpncee-2018.html

MPNCEE2018 Melanoma in CEE 21st- 23th September, Bucharest

Welcome!

Our MPNCEE meetings J

2016, Leuven MPNCEE 2017, Zagreb

Our 2nd MPNCEE conference! 2018, Bucharest

Why MPNCEE? Working Group Melanoma Patient Network Europe

•

A platform of CEE patients and patients advocates – Educate – Connect – Exchange

2018, Bucharest Disease and treatments Staging Our drugs in melanoma Latest developments Adjuvant therapies

Healthcare How to improve Melanoma outcomes Saving melanoma lives Shaping the environment for healthcare: data, collaboration and evidence-based policy

2018, Bucharest Advocacy How do we advocate more effectively? A good strategy in Melanoma Advocacy

Access to melanoma drugs Standard Care or Clinical Trials

Connections Meet, share, learn! All sessions, social events

We like to start with coffee!J q • • •

Friday Welcome coffee 14.00 Conference 13.00-19.00 Dinner 20.00

q • • • •

Saturday Welcome coffee 8.30 Conference 9.00-18.30 Dinner at 18.30 Walk in the old town & Social event 20.30

q • • •

Sunday Welcome coffee 8.30 Conference 9.00-13.00 Lunch 13.00

have a great time! take initiative! â&#x20AC;Śâ&#x20AC;Śand ask the tough questions!

Patient Advocacy Bettina Ryll, MD/ PhD Melanoma Patient Network Europe, Founder

https://www.linkedin.com/pulse/nobody-cares-healthcare-stefan-gijssels/

B. Ryll MPNE 2018

Page 2

Working definition Patient • concerned with own disease Patient advocate (PA) • widened focus on the patient group • in exchange with peers Patient advocate expert (PAE) • PA engaging at a professional level

ESMO PAWG working definition 3

Our network

EU of the 28 • 24 official languages • 5 semi-official languages • about 60 minority languages • according to a Eurobarometer poll in 2012, 38% Europeans speak English and a quarter can read an English newspaper, understand TV news, communicate online in English

• Health both regulated on national (in particular, HTA and reimbursement) and European level (e.g. EMA, DG Santé)

The EF English Proficiency Index 2015

B. Ryll, MPNE

MPNE model-

connecting bi-lingual, English-speaking Melanoma advocates and patients across Europe.

Melanoma patients: network nodes

English speaking network nodes: hubs

B. Ryll, MPNE

MPNE- subsidiarity and parallel innovation The Challenge • problems and healthcare are diverse and complex • we all care about different things • we have a wide range of expertise The problem(s) • problems arise and need to be solved locally • language skills and understanding of culture are critical • health is under national authority Parallel innovation • many people working in parallel means we test many solutions in parallel- as long as we exchange and learn from each other, everyone wins

Principles

Melanoma Patient Network Europe

MPNE principle No1 Patients FIRST.

Our lives have been affected by Melanoma. Our first and foremost concern are Melanoma patients.

MPNE principle No2 Solutions, not problems. The ultimate purpose of health care is to benefit patients. Patients have unique insights and knowledge not shared by other stakeholders. We see it as our responsibility to use our knowledge to find solutions. Solutions that improve the lives of Melanoma patients today and tomorrow.

MPNE principle No3 Data, not opinions. All health-related information on our forums and at our events needs to be supported by evidence. There is no such a thing as â&#x20AC;&#x2DC;the patient voiceâ&#x20AC;&#x2122;. Patient preferences spread naturally. Only data will help us to be fair on each patient. Our approach to advocacy is evidence-based: we support our positions with data. Not opinions.

MPNE principle No4 If you donâ&#x20AC;&#x2122;t do it- no one will. The challenges in Melanoma are as enormous as they are diverse. Fortunately, we are growing network of motivated individuals with an equally diverse skill set. And we enable and support our network members to tackle the problems they care most about.

MPNE education strategy Version 1.1 2017

MPNE education strategy principles 1. Driven by a patientâ&#x20AC;&#x2122;s need and interest provide targeted education addressing the specific needs and interests of each MPNE network member category and in a way that allows learning by interest/ need. 2. Enabling and empowering provide education that empowers and enables European Melanoma advocates to assume personal responsibility and become effective advocates for themselves and others 3. Motivating and forward-thinking supporting and mentoring according to interests and talents every individual who is motivated to improve the situation of the European Melanoma community and who shares MPNE principles; individuals are expected to share and pass on the knowledge they benefited from

Our network members

Melanoma Patient Network Europe Members

who are

MPNEnodes majority

European Melanoma patients and carers mostly concerned with their own disease and with limited connections to others. Motivations for connecting are disease information and support.

MPNEhubs drivers at countrylevel and connectors across Europe

European Melanoma patients and carers connecting MPNEnodes within a country and across country borders; concerned about the larger group, main focus on national level. Motivations for connecting are knowledge and information about Melanoma and its treatments, healthcare systems and like-minded people with interest in advocacy.

MPNEcores drivers at EU-level

European Melanoma patients and carers who are highly connected within and beyond the Melanoma community. Focus and concern is the European Melanoma community. Reasons for connecting are knowledge and information about Melanoma, healthcare systems and political processes; communication, alignment and collaboration.

THE THREE KNOWLEDGE PILLARS

OF SUCCESSFUL MELANOMA PATIENT ADVOCACY

Melanoma

Systems

Tools

THE THREE KNOWLEDGE PILLARS

OF SUCCESSFUL MELANOMA PATIENT ADVOCACY

Melanoma

Systems

What do I have to know about the disease and its treatments? How does the system work?

Tools

Which tools do I need to advocoate successfully?

Educational needs

Melanoma

Systems

Advocacy

understanding disease, therapies and treatment options

understanding healthcare systems and other relevant systems like drug development, research, policy landscape

skills and tools relevant to advocacy such as project management, communication, presentation skills

MPNEnodes

Understanding • Disease and prognosis. • Stage-specific information on therapies and therapeutic choices. • Therapies and side effects • Psychological impact of disease.

Knowing how to • access best care including supportive/ palliative and psychological care • how to report side effects

Knowing how to • advocate for themselves • patients rights • have constructive discussions with medical care team

MPNEhubs

• Disease, stages and effect on prognosis. • Stage-specific information on therapies and therapeutic choices. • Prevention and early detection • Psychological impact of disease.

• understanding and navigating a country’s healthcare system • drug development • how does pharmacovigilance work? Reporting and tracing side effects (e.g. Vigiaccess)

• How to access relevant medical information • How to build national Melanoma groups (organisation, programs, funding) • building and managing patient forums • presentation skills

MPNEcores

• Melanoma- disease, therapies, therapeutic choices according to stage and circumstances • effective prevention and early detection measures • psychological impact of disease

• differences between national healthcare systems • EU impact on national healthcare systems • trans-national health initiatives

• • • •

leadership skills presentation skills overview of existing initiatives network building

Thank you and have a great weekend! www.melanomapatientnetworkEU.org

KNOW YOUR STAGE!

Translating pTNM into prognosis and treatment options

Violeta Astratinei and Gilly Spurrier Melanoma Patient Network Europe MPNCEE2018, September 2018 Bucharest Up-to-date as of March 2018 To be revised March 2019

Staging describes the â&#x20AC;&#x2DC;stageâ&#x20AC;&#x2122; of a

disease, so how far the Melanoma has spread in the body.

Up-to-date as of March 2018 To be revised March 2019

Melanoma staging for patients, by Bettina Ryll, September 2017

How far a Melanoma has exactly spread anatomically is described as ‘TNM’ which stands for: ❏

the Tumour (size and whether the surface is broken (ulceration)

❏

the Lymph

❏

distant

Nodes

that have been affected

Metastasis (the cancer has spread to

another part of the body)

This is called the TNM classification - AJCC Up-to-date as of March 2018 To be revised March 2019

Melanoma staging for patients, by Bettina Ryll, September 2017

Stage 1

Tumour thickness and ulceration No nearby nodes No metastasis

pTN0M0

Up-to-date as of March 2018 To be revised March 2019

Anca

Up-to-date as of March 2018 To be revised March 2019

Stage 1: IA, IB Thickness

IA IB

T1a T1b

T2a

Ulceration

< 0.8mm <0.8mm

No Yes

N0 N0

M0 M0

0.8-1.0mm

Either

1.0-2.0mm

Never nearby lymph nodes Never metastasis Up-to-date as of March 2018 To be revised March 2019

Stage 2

Tumour thickness and ulceration

pTN0M0

Up-to-date as of March 2018 To be revised March 2019

Imogen pT4bN0Mx

Up-to-date as of March 2018 To be revised March 2019

Stage 2 : IIA, IIB, IIC Thickness

Ulceration

T2b T3a

>1-2.0mm >2-4mm

Yes No

N0 N0

M0 M0

T3b T4a

>2-4mm >4mm

Yes No

N0 N0

M0 M0

T4b

>4mm

Yes

M0 Never nearby lymph nodes Never metastasis

Stage 3 Nearby lymph nodes

pTNM0

Up-to-date as of March 2018 To be revised March 2019

Koen pT3bN2bM0

Up-to-date as of March 2018 To be revised March 2019

Stage 3 : IIIA, IIIB, IIIC, IIID N1a N1b N1c N2a N2b N2c N3a N3b N3c

Nodes In transit/satellites 1 Clinically Occult No M0 1 Clinically Detected No M0 0 Yes M0 2-3 Clinically Occult No M0 2-3 1 Clinically Detected No M0 1 Clinically Occult or Detected Yes M0 4+ Clinically Occult No M0 4+ of which 1Cln Dt + Matted Nodes No M0 2+ Cln Oc or Cln Dt +Matted nodes Yes M0

Cln Oc - Clinically occult -microscopic metastasis confirmed by SLN biopsy Cln Dt - Clinically detected - metastasis that can be ‘seen’ clinically, by ultrasound or radiographic Matted nodes - nodes deﬁned as 2 or more nodes adherent to one another Up-to-date as of March 2018 To be revised March 2019

Stage 3 Subgroups

Click to add text

Up-to-date as of March 2018 To be revised March 2019

Stage 4

Spread beyond regional lymph nodes Location of metastases and LDH level

pTNM

Up-to-date as of March 2018 To be revised March 2019

Lucy pT2aN1M1c

Up-to-date as of March 2018 To be revised March 2019

Stage 4 Melanoma Sites of metastasis M1a(0) Skin, Subcutaneous tissue,

Up-to-date as of March 2018 To be revised March 2019

LDH

Muscles, Distant LN

Normal

M1a(1) M1b(0) Lung M1b(1) M1c(0) Any other Visceral (not CNS) M1c(1) M1d(0) Any CNS site M1d(1)

Raised Normal Raised Normal Raised Normal Raised

Main Changes in staging in AJCC 8th edition

• • •

0.8mm threshold for T1 Mitotic Rate removed Tis = In situ, T0 = unknown primary

• •

Micro & Macro Nodes : now clinically occult or clinically detected N Category has now 4 subsets : IIIA, IIIB, IIIC & IIID

• •

M Category has new M1D for brain metastasis M category include now subgroups for normal (0) or elevated (1) LDH

From 1st January 2018, Melanoma patients are staged according to AJCC 8th edition.

Reference Detailed description of the AJCC Melanoma staging 8th edition - valid from 1st Jan 2018

Gershewald et al (2017)- Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual http://onlinelibrary.wiley.com/doi/10.3322/caac.21409/full

Up-to-date as of March 2018 To be revised March 2019

KNOW YOUR DRUGS! EU-approved Melanoma treatments in 2018

Bettina Ryll, MD/PhD

Melanoma Patient Network Europe MPNCEE2018, September 2018 Bucharest Up-to-date as of March 2018 To be revised March 2019

The EMA website- great resource for drug information

http://www.ema.europa.eu/ema/

The years that changed everything in Melanoma Nivolumab

Nivolumab Interleukin-2

2011 2012

2013

2014

2015

2016

2017

2018

Trametinib Vemurafenib Debrafenib

Melanoma The Dark Ages

Nivolumab + Ipilimumab

Pembrolizumab

Ipilimumab

DTIC

adjuvant

T-Vec

Debrafenib + Trametinib Vemurafenib + Cobimetinib

Encorafenib + Binimetinib Debrafenib + Trametinib adjuvant

Approval of medicines: the label ● ● ● ●

Which drug in which dose: how much how often Indication: which patients will receive it (e.g. age, diagnosis, Stage 4, Stage 3) other conditions (e.g. 1st line or 2nd line, brain mets, other conditions)

all to be found on the EMA website!

If used differently from approved label- off-label use

EU- approved Melanoma drugs Targeted therapies

Immune therapies

BRAF inhibitors

BRAFmut only

Checkpoint inhibitors

• Vemurafenib

oral therapies = tablets

• Ipilimumab

work fast

• Nivolumab

• Dabrafenib • Encorafenib MEK inhibitors • Trametinib • Cotellic • Binimetinib

most patients respond tumours become resistant no more drug, no more effect, no more side effect

• Pembrolizumab

Modified virus • T-Vec

all Melanomas perfusions = i.v. only take time to work not every patient responds no more drug, still effects and side effects possible

Targeted therapies- of lawn mowers, broken switches and traffic jams.

Checkpoint inhibitors- blocked brakes.

CTL 4, PD1

The drug ’spec sheets’ • ORR- overall response rate (partial plus complete response) • PSF- progression-free survival (time till disease comes back) • OS- overall survival (what we all want)

good description of endpoints: http://theoncologist.alphamedpress.org/content/13/suppl_2/19.full

SUMMARY

Refs.

all you want to know, 2017

Know your drugs and have a great weekend! www.melanomapatientnetworkEU.org

ASCO 2018 Bettina Ryll, MD/PhD

Melanoma Patient Network Europe MPNCEE2018, September 2018 Bucharest Up-to-date as of March 2018 To be revised March 2019

my personal ’take-homes’

http://mpneatasco2018.blogspot.com/

Long-term survival in Stage 1A and 1B Important points •

• •

The time frame in Melanoma is important: Melanoma can always come back Melanoma is dangerous, even at a very early stage Earlier detection will save lives

Ref- https://link.springer.com/article/10.1245%2Fs10434-017-6325-1 5

some key points

1. immune therapy shows amazing results- but not for every patient.

Significant clinical activity â&#x20AC;&#x201C; but not for all patients

Broad Pan-Tumor Potential with anti-PD-L1/PD-1 inhibitors monotherapy Unselected patients Modified from D. Chen, BioScience Forum, 2015

2. Many factors contribute to a successful immune response.