www.emccc2019.org

9th European Multidisciplinary Colorectal Cancer Congress

9-11 MARCH 2019Lisbon Congress Center

Portugal

PROGRAM

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WELCOME

We are delighted to welcome you to the 9th European Multidisciplinary Colorectal Cancer Congress 2019!

The European Multidisciplinary Colorectal Cancer Congress (EMCCC) is the European conference that truly provides a platform for in-depth multidisciplinary interaction among the various research areas involved. The Dutch Colorectal Cancer Group (DCCG) has taken the initiative for the EMCCC since 2001. The conference in 2019 builds upon eight previous successful multidisciplinary conferences on colorectal cancer which were held in the Netherlands, Germany and France.

The EMCCC offers an intimate scientific/educational environment. Colorectal cancer is one of the most common types of malignancies and much progress has been made in recent years in understanding the biology and treatment of this disease. These developments encompass almost the full research area including genetics, biology, pathology/prognostic markers, surgery, screening, systemic treatment, radiotherapy, and imaging. This implies that both pre-clinical and clinical research is becoming much more multidisciplinary oriented. The conference will have separate workshops on surgery, medical oncology, radiotherapy, pathology, imaging, gastro enterology, and genetics, but all other sessions are plenary in order to have optimal interaction between all disciplines.

EMCCC 2019 Organizing committeePieter Tanis (Surgery, DCCG) Dirk Arnold (Medical Oncology, EORTC) Helder Mansinho (Medical Oncology, GICD) Miriam Koopman (Medical Oncology, DCCG) Jeroen Buysen (Radiotherapy, DCCG) Rolf Sijmons (Genetics, DCCG) Leon Moons (Gastroenterology, DCCG) Regina Beets-Tan (Radiology, DCCG)

The 9th EMCCC 2019 is endorsed by:

An ESO Recommended Event

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13:00 – 13:05 OpeningAuditorium 2

13:05 – 14:30 Lessons to be learned from national and international research infrastructures Chairs: Dirk Arnold, Helder Mansinho

13:05 Dutch T1 CRC working group Leon Moons, the Netherlands

13:12 French GRECCAR Study Group Quentin Denost, France

13:19 National Cancer Research Institute - Colorectal Cancer Clinical Studies Group Richard Adams, United Kingdom

13:26 Danish Colorectal Cancer Group Lene Iversen, Denmark

13:33 Dutch Colorectal Cancer Group // PLCRC Pieter Tanis & Geraldine Vink, the Netherlands

13:47 Italian Intergroup structure and projects Sara Lonardi, Italy

13:54 German AIO group Volker Heinemann, Germany

14:01 Lessons to be learned from national and international research infraestructures -Portuguese GICD study group

Hélder Mansinho, Portugal

14:08 EORTC GI group Marc Peeters, Belgium

14:15 Discussion

14:30 – 15:00 Break 15:00 – 16:00 Sponsored symposium Servier See page 17

16:00 – 18:00 Discussing areas of controversy Chair: Hans de Wilt

16:00 In primary treatment rectal cancer David Sebag Montefiore, United Kingdom

SATURDAY 9 MARCH

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16:25 In primary treatment colon cancer Pieter Tanis, the Netherlands

16:50 What is known and where are the major needs? In local treatments of metastases Interventional Radiology

Kees Verhoef, the Netherlands

17:05 In local treatments of metastases Interventional Radiology Martijn Meijerink, the Netherlands

17:20 Local treatments in Colorectal metastasis: the role of radiotherapy. State of art and future prospective

Veronica Dell’Acqua, Italy

17:35 In systemic treatment Dirk Arnold, Portugal

17:50 Discussion

18:00 – 18:30 DCCG lecture Chairs: Dirk Arnold, Pieter Tanis

18:00 Colon cancer: What is the best approach to understand the disease? Louis Vermeulen, the Netherlands

18:30 – 19:30 Welcome reception

SATURDAY 9 MARCH

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08:15 – 09:30 Session 1: Challenges in screen detected early cancersAuditorium 2 Chair: Leon Moons

08:15 S1.1 Prediction models for lymph node metastasis Miangele Lacle, the Netherlands

08:35 S1.2 Screen detected early cancers: evaluation of the resection margin- is 1 mm sufficient?

Maurice Loughrey, Ireland

08:55 S1.3 What is coming next in the prediction of LNM- Cord Langner, Austria

09:15 Discussion

09:30 – 10:45 Session 2: What’s new in diagnostic imaging – and what are the therapeutic consequences?

Chairs: Regina Beets-Tan, Pieter Tanis

09:30 S2.1 Locoregional staging of colon and rectal cancer Regina Beets-Tan, the Netherlands

09:50 S2.2 Imaging modalities for liver metastases Doenja Lambregts, the Netherlands

10:10 S2.3 New diagnostic tools: radiomics, “deep learning” – really helpful? Philippe Lambin, the Netherlands

10:30 Discussion

10:30 – 16:30 PARALLEL PROGRAM – GASTROENTEROLOGY See page 11

10:45 – 11:15 Break

11:15 – 12:30 Session 3: State of the art and development in neo-adjuvant treatment Chairs: Jeroen Buijsen, Kees Verhoef

11:15 S3.1 Difference between cCR after CRT for advanced rectal cancer and aiming for cCR with CRT in early rectal cancer

Rob Glynne-Jones, United Kingdom

11:35 S3.2 Is chemotherapy going to replace radiotherapy in rectal cancer? David Sebag Montefiore, United Kingdom

11:55 S3.3 Deciding on further local treatment after induction therapy for local and metastatic disease; value and timing of re-staging modalities

Geerard Beets, the Netherlands

SUNDAY 10 MARCH

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12:15 Discussion

12:30 – 14:00 Lunch & Poster Presentations (odd numbers)

12:45 – 13:45 CRC Group Meetings / Trial Meetings / Consensus or Guideline initiatives

12:45 B1.1 InterAACT: A global initiative in anal cancerroom 1.05 Sheela Rao, United Kingdom

12:45 B1.2 Presentation of CIREL and CIEMAR registriesroom 1.06 Philippe Pereira, Germany

12:45 B1.3 Translational research: from bench to bedside and backroom 1.07 Chair: Onno Kranenburg

12:45 B1.3.1 From Tissue towards Liquid biopsy: current status Marc Peeters, Belgium

13:00 B1.3.2 The serrated pathway: implications for research Iris Nagtegaal, the Netherlands

13:15 B1.3.3 Organoid models to improve intraperitoneal chemotherapy Onno Kranenburg, the Netherlands

13:30 B1.3.4 Circulating tumor DNA as biomarker in colorectal cancer: turning research into care

Remond Fijneman, the Netherlands

14:00 – 15:00 Session 4: Case discussion with expert panel Expert panel: Kees Verhoef, Marc Peeters, Hugo Pinto Marques, Gero

Puhl, Sara Lonardi, Pieter Tanis

14:00 S4.1 Case on the edge of liver surgery for mCRC Hugo Pinto Marques, Portugal

14:15 S4.2 Case on the edge of multimodality treatment of mCRC Gero Puhl, Germany

14:30 Panel discussion

15:00 – 16:00 Session 5: Translational research: From markers to decisions Chairs: Onno Kranenburg, Karen-Lise Garm Spindler

15:00 S5.1 Clinical implications of “liquid” markers (ctDNA) for treatment selection and response evaluation

Karen-Lise Spindler, Denmark

SUNDAY 10 MARCH

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15:20 S5.2 Molecular subtypes in colorectal cancer: CMS and beyond Louis Vermeulen, the Netherlands

15:40 S5.3 Organoids to assess treatment response Nicola Valeri, United Kingdom

16:00 – 16:30 Break

16:30 – 17:45 Session 6: What’s new in diagnostic and therapeutic endoscopy? Chairs: Leon Moons, Pieter Tanis

16:30 S6.1 State of the art optical diagnosis of polyps Yara Backes, the Netherlands

16:50 S6.2 Endoscopic and surgical techniques for local excision in rectal cancer, what should we do? Fransico Baldaque Silva, Sweden

17:10 S6.3 Endoscopic and hybrid techniques for local excision of colon cancer Leon Moons, the Netherlands

17:30 Discussion

19:00 Dinner See page 14

SUNDAY 10 MARCH

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08:15 – 09:30 Session 7: Future of primary rectal cancer treatmentAuditorium 2 Chair: Kees Verhoef

08:15 S7.1 Role of external beam and endoluminal radiation boosting in rectal cancer Maaike Berbeé, the Netherlands

08:35 S7.2 Challenges in rectal cancer surgery; which problems have to be solved? Roel Hompes, the Netherlands

08:55 S7.3 Locally recurrent rectal cancer; multimodality approach Quentin Denost, France

09:15 Discussion

09:30 – 10:45 Session 8: Systemic therapy in the metastatic setting – state of the art and future

Chairs: Richard Adams, Hugo Pinto Marques

09:30 S8.1 Targeting RAS mutated tumors Volker Heinemann, Germany

09:50 S8.2 Prognostic/predictive value of molecular and clinical factors: What makes the difference?

Teresa Macarulla, Spain

10:10 S8.3 Feasibility and outcomes of a national expert panel to determine secondary resectability in patients with initially unresectable colorectal liver metastases (CRLM)

Karen Bolhuis, the Netherlands

10:30 Discussion

09:45 RADIOLOGY PARALLEL PROGRAM See page 12

10:45 – 11:15 Break

11:15 – 12:30 Session 9: Colorectal cancer and the immune system Chair: Dirk Arnold

11:15 S9.1 What are the new drugs in the field of immunotherapy? Guillem Argiles, Spain

11:35 S9.2 What are the diagnostic tools and novel concepts of cancer evolution? Jerome Galon, France

11:55 S9.3 What are the effects that are interfering with local or current treatments? Miriam Chalabi, the Netherlands

12:15 Discussion

12:30 – 14:00 Lunch & Poster Presentations (even numbers)

MONDAY 11 MARCH

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MONDAY 11 MARCH

12:45 – 13:45 Best abstract sessionAuditorium 2 Chairs: Rolf Sijmons, Jeroen Buijsen

12:45 O0.1 Circulating tumor DNA as a marker of minimal residual disease following local treatment of metastases from colorectal cancer

Anders Boysen, Denmark

12:55 O0.2 Outcomes of J-pouch vs side-to-end vs end-to-end colorectal anastomoses after total mesorectal excision for rectal carcinoma: a prospective trial

Arsen Rasulov, Russia

13:05 O0.3 Brachytherapy boost for rectal cancer as a part of curative treatment - retrospective study

Manuel Louro, Portugal

13:15 O0.4 Is decompressing stoma a better alternative than stent as bridge to surgery for left-sided obstructive colon cancer

Joyce Veld, the Netherlands

13:25 O0.5 The role of induction chemotherapy as an addition to the neoadjuvant treatment for locally recurrent rectal cancer

Eva Voogt, the Netherlands

13:35 O0.6 MR-Guided radiation therapy fo locally advanced rectal (LARC) cancer by Mridian?: A monoinstitutional experience and future perspectives

Giuditta Chiloiro, Italy

14:00 – 15:15 Session 10: Genetics Chairs: Rolf Sijmons, Richard Houlston

14:00 S10.1 Update: the genetic differential diagnosis of polyposis and CRC Maartje Nielsen, the Netherlands

14:20 S10.2 Predicting CRC risk: from tumor syndromes genes to polygenic risk scores Richard Houlston, United Kingdom

14:40 S10.3 The Immune Evolution of Hereditary Colorectal Cancers - New Concepts and Clinical Implications

Matthias Kloor, Germany

15:00 Discussion

15:15 – 15:45 Break

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15:45 – 17:00 Session 11: Curative treatment of metastases Chairs: Eduardo Barosso, Pieter Tanis

15:45 S11.1 Controversies in loco-regional therapy of peritoneal metastases: What is really needed?

Niels Kok, the Netherlands

16:05 S11.2 Liver-directed therapies (Hepatic arterial infusion, SIRT): What to use when? Bas Groot Koerkamp, the Netherlands

16:25 S11.3 Spectrum of treatments for lung metastases: SBRT, RFA, resection or no local therapy at all?

Dirk Van Raemdonck, Belgium

16:45 Discussion

17:00 Closing

MONDAY 11 MARCH

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Sunday 10 March Meetingroom 1.08

10:30 – 12:30 Pathology

10:30 G1.1 Should Tumor budding be included in the risk prediction algorithms Alessandro Lugli, Switzerland

11:00 G1.2 Evolution to early carcinoma-lessons for lymph node metastasis Lennard Lee, United Kingdom

11:30 G1.3 What is a sufficient resection margin Maurice Loughrey, Ireland

12:00 G1.4 Observer variation for histologic risk predictors Miangele Lacle, the Netherlands

12:30 – 14:00 Lunch

14:00 – 15:45 Resection

14:00 G1.5 Cut-off level for en bloc resections? Yara Backes, the Netherlands

14:30 G1.6 ESD or TEM/TAMIS? Eelco de Graaf, the Netherlands

15:00 G1.7 eFTR, ESD or limited surgical wedge excision Francisco Baldaque Silva, Sweden

15:30 G1.8 Wait and see of high risk T1 CRCs Regina Beets-Tan & Roel Hompes, the Netherlands

GASTROENTEROLOGY PARALLEL PROGRAM

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Monday 11 March

Meetingroom 1.08

09:45 – 10:45 Workshop on imaging of rectal cancer, lectures, interactive case based discussions

09:45 R1.1 Organ preservation: the surgeon’s view Geerard Beets, the Netherlands

10:05 R1.2 Diffusion weighted MRI and its role in Organ preservation Doenja Lambregts, the Netherlands

10:25 R1.3 Radiomics in rectal cancer Joost van Griethuysen, the Netherlands

10:45 – 11:15 Break

11:15 – 12:30 Case based panel discussions

12:30 – 14:00 Lunch

14:00 – 15:15 Workshop on imaging and treatment of colorectal Liver metastases

14:00 R1.4 Image evaluation of advanced colorectal cancer in the era of targeted and locoregional therapies

Riccardo Manfredi, Italy

14:20 R1.5 New trends in the systemic treatments of advanced colorectal cancer Andres Cervantes, Spain

14:40 R1.6 Navigation surgery and open ablative therapies in colorectal metastases in the liver

Theo Ruers, the Netherlands

15:00 R1.7 The role of interventional radiology out of the guidelines for patatients with metastatic colorectal cancer

Fernando Gómez Muñoz, Spain

RADIOLOGY PARALLEL PROGRAM

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DOWNLOAD THE OFFICIAL EMCCC APP

The EMCCC 2019 Congress App can be downloaded from the App store (Apple) or Google Play Store (Android) at no costs. You can download the app in four simple steps:

1 Go to the Appstore or Google Playstore and search for ‘Congress Care’

2. Install and open the app on your phone or tablet.

3. Select the event EMCCC and click on ‘install’

4. The app is now ready for use

In this App you will find a detailed overview of:• The scientific program

including summaries • Posters and abstracts• Author index • Sponsors • General information such as

accreditation, social events, opening hours registration desk etc.

For assistance and questions regarding the App, please see the staff at the registration desk.

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Welcome receptionOn Saturday 09 March 2019 the welcome reception will take place at the Lisbon Congress Center, from 18:30 – 19:30 hrs.

The welcome reception is included in the conference fee.

Congress dinnerThe congress dinner (ticketed) will be held at the Páteo Alfacinha on Sunday 10 March 2019, from 19:00 hrs for registered delegate only. In case you are registered for the congress dinner, a dinner icon is printed on your badge.

Páteo Alfacinha is a special place near the area of Belém which recreates a small Lisbon courtyard, surrounded by small typical houses. This lovingly crafted recreation includes small traditional “shops”, such as a bakery, a tavern, a chapel as well as some simple living quarters.

Busses will depart as of 19:00 hrs. from Hotel Vila Galé Ópera and Hotel Pestana Palace Lisboa. For the final departure times, please see the staff at the registration desk.

SOCIAL PROGRAM

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Congress venueLisboa Congress CenterPraça das Indústrias nº11300-307Lisbon, Portugal

Opening hours registration/information deskSaturday 9 March 12:00-18:30Sunday 10 March 07:45-17:30Monday 11 March 07:45-17:00

NamebadgeParticipants should collect name badges from the conference registration desk. Since only registered participants will be permitted to attend the scientific sessions, the exhibition and poster areas, you are kindly asked to wear your badge when entering the congress venue.Exhibitors will also receive badges to allow access to the respective areas.

Poster presentationsAll posters are situated at the poster area, Pavillion 4. The poster area is open to all participants during the entire congress. The numbers on the poster panels correspond with the abstract numbers in the app.

Poster mounting / Removal: Poster mounting: Saturday 9 March from 13:00 - 19:00 hrs. and on Sunday 10 March from 08:00 - 10:30 hrs. Poster removal: Monday 11 March after 15:45 hrs. Posters that not have been removed by the author on Monday 11 March 18:00 hrs. are removed and disposed.

Presentation of your poster: - ODD poster numbers: Sunday 10 March 2019 from 13:00 – 14:00 hrs. - EVEN poster numbers: Monday 11 March 2019 from 13:00 - 14:00 hrs.

EMCCC Social mediaEMCCC can be followed on Twitter, via @emccc2019. If you would like to share your tweets with other delegates following EMCCC 2019, please use #EMCCC2019.Follow EMCCC2019 on Facebook via www.facebook.com/EMCCC2019 and Linkedin via https://bit.ly/2IhdDdz

WIFISSID: EMCCC 2019Password: Lisbon19

GENERAL INFORMATION

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AccreditationThe 9th European Multidisciplinary Colorectal Cancer Congress, Lisbon, Portugal, 09/03/2019 – 11/03/2019 has been accredited by the European Accreditation Council for Continuing Medical Education (EACCME®) with 20 European CME credits (ECMEC®s). Each medical specialist should claim only those hours of credit that he/she actually spent in the educational activity.Through an agreement between the Union Européenne des Médecins Spécialistes and the American Medical Association, physicians may convert EACCME® credits to an equivalent number of AMA PRA Category 1 CreditsTM. Information on the process to convert EACCME® credit to AMA credit can be found at www.ama-assn.org/education/earn-credit-participation-international-activities.Live educational activities, occurring outside of Canada, recognised by the UEMS-EACCME® for ECMEC®s are deemed to be Accredited Group Learning Activities (Section 1) as defined by the Maintenance of Certification Program of the Royal College of Physicians and Surgeons of Canada.

Maximum credits per day: 09.03.2019 – 6,0010.03.2019 – 8,0011.03.2019 – 6,00

Certificate of attendanceCertificates of attendance will be sent after the congress within two weeks by email.

Congress languageThe official language of the congress will be English. No simultaneous translation will be available.

InsuranceIn registering for EMCCC 2019, delegates agree that neither the organisation nor thecongress agency Congress Care is responsible for individual medical, travel or personalinsurance. Delegates are requested to make their own travel and health insurance.The organizers cannot assume liability for changes.

SecretariatCongress CarePo Box 440NL-5201 AK, ’s-HertogenboschThe NetherlandsTel. +31 (0)73 690 14 15www.congresscare.comemccc@congresscare.cominfo@congresscare.com

GENERAL INFORMATION

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Date: Saturday 9 March, 2019 Time: 15:00-16:00Location: Auditorium 2

Management of 3rd line mCRC – a continuous evolving areaChairpersons: H. Mansinho (Portugal), M. Peeters (Belgium)

IntroductionH. Mansinho (Portugal)

Measures to take for the presenting mCRC patientA. Raimundo (Portugal)

Treatment options and sequence in mCRC patients beyond 2nd lineM. Peeters (Belgium)

Panel discussion based on 2 patient cases from real lifeH. Mansinho (Portugal), M. Peeters (Belgium), A. Raimundo (Portugal)

Discussion and conclusionH. Mansinho (Portugal)M. Peeters (Belgium)

SPONSORED SYMPOSIUM SERVIER

SPONSORS

Major sponsor

Sponsors

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Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie

40 Years of

Excellence

Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie

International Journal of Cancer Research and Treatment

Topical Karger JournalsAn international platform for key opinions and research

EditorsJ.-Y. Fang, ShanghaiP. Malfertheiner, Munich

This international, peer-reviewed journal brings together the leading opinions in all fi elds related to gastrointestinal cancer research. Topics featured range from the identifi cation of new therapeutic targets to epidemiology, disease prevention, treatment and patient management.

www.karger.com/gat

Focusing on clinical and translational research

Editor-in-ChiefM. Hallek, Cologne

Oncology Research and Treatment off ers an interdisciplinary forum for cancer research and treatment and is addressed to clinicians and practitioners working and researching in the fi eld of hematology and oncology.

www.karger.com/ort

Your source for important clinical and translational laboratory studies from around the world

Editor-in-ChiefM. Markman, Philadelphia, PA

This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation, to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease.

www.karger.com/ocl

Now indexed in PubMed

KI19

111

Your first choice for 3rd line mCRC

HARNESSTHE POWER OF

STIVARGA® (regorafenib)Maximize overall survival (OS)

potential for patients withgood performance status

in 3rd line metastaticcolorectal cancer (mCRC)

STIVARGA efficacy in the 3rd-line treatment of mCRCwas proven in over 7,400 patients in both phase 3, randomized,

controlled trials and real-world studies1-12

Nome: Stivarga. Composição: Cada comprimido revestido por película contém 40 mg de regorafenib. Forma Farmacêutica: Comprimido revestido por película. Indicações terapêuticas: Em monoterapia é indicado para o tratamento de doentes adultos com: cancro colorectal (CCR) metastático que foram previamente tratados com, ou não são considerados elegíveis para as terapêuticas disponíveis. Estas incluem quimioterapia à base de fluoropirimidinas, uma terapêutica anti-VEGF e uma terapêutica anti-EGFR; tumores do estroma gastrointestinal (GIST) não ressecáveis ou metastáticos que progrediram ou que são intolerantes ao tratamento prévio com imatinib e sunitinib; carcinoma hepatocelular (CHC) que foram previamente tratados com sorafenib. Posologia e modo de administração: A dose recomendada é de 160 mg de regorafenib (4 comprimidos de 40 mg), tomada uma vez por dia, durante 3 semanas seguida de 1 semana sem terapêutica. Este período de 4 semanas é considerado um ciclo de tratamento. Podem ser necessárias interrupções da administração e/ou diminuições da dose com base na segurança e tolerabilidade individuais. As alterações da dose têm de ser aplicadas por etapas, em doses de 40 mg (um comprimido). A dose diária mais baixa recomendada é de 80 mg. A dose diária máxima é de 160 mg. Não é recomendada a utilização em doentes com compromisso hepático grave (Child-Pugh C).Não são necessários ajustes posológicos: doentes com compromisso hepático ligeiro; doentes com compromisso renal ligeiro ou moderado; com base no sexo; com base na etnia. Stivarga é para utilização por via oral e deve ser tomado à mesma hora todos os dias. Os comprimidos devem ser engolidos inteiros com água após uma refeição ligeira contendo menos de 30% de gordura. Contraindicações: Hipersensibilidade à substância ativa ou a qualquer um dos excipientes. Advertências e precauções especiais de utilização: Efeitos hepáticos: Recomenda-se que sejam realizados testes da função hepática; Doentes com síndrome de Gilbert; Doentes com compromisso hepático ligeiro ou moderado, Hemorragia; Isquemia cardíaca e enfarte do miocárdio; Síndrome de encefalopatia posterior reversível (SEPR); Perfuração e fístula gastrointestinais; Hipertensão arterial; Complicações da cicatrização de ferida; Toxicidade dermatológica; Anomalias dos testes laboratoriais bioquímicos e metabólicos. Em casos de agravamento de eventos de infecção deve considerar-se a interrupção do tratamento de Stivarga. Recomenda-se a interrupção de Stivarga em doentes que desenvolvam perfuração ou fístula gastrointestinal. Interações medicamentosas: Inibidores do CYP3A4 e UGT1A9 / indutores do CYP3A; Substratos da UGT1A1 e da UGT1A9; Substratos da Proteína de Resistência do Cancro da Mama (Breast Cancer Resistance Protein - BCRP) e da glicoproteína-P; Inibidores da glicoproteína-P e da BCRP/Indutores da glicoproteína_P e da BCRP; Substratos seletivos de isoformas CYP; Antibióticos; Agentes sequestrantes dos sais biliares. Efeitos indesejáveis: Infeção; Trombocitopenia; Anemia; Diminuição do apetite e da ingestão de alimentos; Cefaleias; Hemorragia; Hipertensão; Disfonia; Diarreia; Estomatite; Vómitos; Naúseas; Hiperbilirrubinemia; Reação cutânea mão-pé; Erupção cutânea; Alopecia; Astenia/Fadiga; Dor; Febre; Inflamação das mucosas; Perda de peso; Leucopenia; Hipotiroidismo; Hipocaliemia; Hipofosfatemia; Hipocalcemia; Hiponatremia; Hipomagnesemia; Hiperuricemia; Tremores; Neuropatia periférica; Perturbações do paladar; Boca seca; Refluxo gastroesofágico; Gastroenterite; Aumento das transaminases; Pele seca; Erupção cutânea esfoliativa; Espasmos musculares; Proteinúria; Aumento da amílase; Aumento da lípase; Razão normalizada internacional anormal; Reação de hipersensibilidade; Enfarte do miocárdio; Isquemia do miocárdio; Crise hipertensiva; Perfuração gastrointestinal; Fístula gastrointestinal; Pancreatite, Lesão hepática grave; Afeção ungueal; Eritema multiforme; Queratoacantoma/ Carcinoma de células escamosas da pele; Síndrome de encefalopatia posterior reversível (SEPR), Síndrome Stevens-Johnson, Necrólise epidérmica tóxica. Número da A.I.M.: 5579479. Data de revisão do texto: 08/2018. Medicamento sujeito a receita médica restrita, de utilização reservada a certos meios especializados. Para mais informações, deverá contatar o Titular da Autorização de Introdução no Mercado. Notifique acontecimentos adversos a: INFARMED (farmacovigilancia@infarmed.pt), Bayer Portugal (medical@bayer.com). Bayer Portugal, Lda. Rua Quinta do Pinheiro 5, 2794-003 Carnaxide. NIF: 500043256

1. STIVARGA (regorafenib) summary of product characteristics [global prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals. 2. Grothey A, Van Cutsem E, Sobrero A, et al; for the CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-312. 3. Li J, Qin S, Xu R, et al; on behalf of the CONCUR Investigators. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619-629. 4. Bendell J, Ciardiello F, Tabernero J, et al. Efficacy and safety results from IMblaze370, a randomised phase III study comparing atezolizumab + cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer. PowerPoint Presented at: European Society for Medical Oncology (ESMO) 20th World Congress on Gastrointestinal Cancer; June 20-23, 2018; Barcelona, Spain. 5. Ducreux M, Petersen LN, Öhler L, et al; on behalf of the CORRELATE Investigators. Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice: final analysis from the prospective, observational CORRELATE study. Presented at: European Society for Medical Oncology (ESMO) 20th World Congress on Gastrointestinal Cancer; June 20-23, 2018; Barcelona, Spain. Poster O-012. 6. Adenis A, de la Fouchardière C, Paule B, et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer. 2016;16:412. 7. Van Cutsem E, Martinelli E, Cascinu S. et al. Regorafenib for Patients with Metastatic Colorectal Cancer Who Progressed After Standard Therapy: Results of the Large, Single-Arm, Open-Label Phase IIIb CONSIGN Study. The Oncologist. 2018;23:1-8. 8. Bekaii-Saab TS, Ou F-S, Anderson DM, et al. Regorafenib dose optimization study (ReDOS): randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC) - an ACCRU Network study. Poster presented at: American Society of Clinical Oncology (ASCO) 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA. 9. Komatsu Y, Muro K, Yamaguchi K, et al. Safety and efficacy of regorafenib post-marketing surveillance (PMS) in Japanese patients with metastatic colorectal cancer (mCRC). J Clin Oncol. 2017;35(suppl):abstract 721-721. American Society of Clinical Oncology (ASCO) 2017 Gastrointestinal Cancers Symposium; June 2-6, 2018; Chicago, Illinois. Abstract 721. 10. Kopeckova K, Chloupkova R, Melichar B, et al. Regorafenib for metastatic colorectal carcinoma: a registry based analysis. Poster presented at: European Society for Medical Oncology (ESMO) 18th World Congress on Gastrointestinal Cancer; October 19-23, 2018; Munich, Germany. Abstract 468P. 11. Kudo T, Kato T, Kagawa Y, et al. Phase II dose titration study of regorafenib for patients with unresectable metastatic colorectal cancer that progressed after standard chemotherapy. Poster presented at: American Society of Clinical Oncology (ASCO) 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA. Abstract 821. 12. Schulz H, Janssen J, Strauss UP, et al. Clinical efficacy and safety of regorafenib (REG) in the treatment of metastatic colorectal cancer (mCRC) in daily practice in Germany: Final results of the prospective multicentre non-interventional RECORA study. Poster presented at: American Society of Clinical Oncology (ASCO) 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA.

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19Your first choice for 3rd line mCRC

HARNESSTHE POWER OF

STIVARGA® (regorafenib)Maximize overall survival (OS)

potential for patients withgood performance status

in 3rd line metastaticcolorectal cancer (mCRC)

STIVARGA efficacy in the 3rd-line treatment of mCRCwas proven in over 7,400 patients in both phase 3, randomized,

controlled trials and real-world studies1-12

Nome: Stivarga. Composição: Cada comprimido revestido por película contém 40 mg de regorafenib. Forma Farmacêutica: Comprimido revestido por película. Indicações terapêuticas: Em monoterapia é indicado para o tratamento de doentes adultos com: cancro colorectal (CCR) metastático que foram previamente tratados com, ou não são considerados elegíveis para as terapêuticas disponíveis. Estas incluem quimioterapia à base de fluoropirimidinas, uma terapêutica anti-VEGF e uma terapêutica anti-EGFR; tumores do estroma gastrointestinal (GIST) não ressecáveis ou metastáticos que progrediram ou que são intolerantes ao tratamento prévio com imatinib e sunitinib; carcinoma hepatocelular (CHC) que foram previamente tratados com sorafenib. Posologia e modo de administração: A dose recomendada é de 160 mg de regorafenib (4 comprimidos de 40 mg), tomada uma vez por dia, durante 3 semanas seguida de 1 semana sem terapêutica. Este período de 4 semanas é considerado um ciclo de tratamento. Podem ser necessárias interrupções da administração e/ou diminuições da dose com base na segurança e tolerabilidade individuais. As alterações da dose têm de ser aplicadas por etapas, em doses de 40 mg (um comprimido). A dose diária mais baixa recomendada é de 80 mg. A dose diária máxima é de 160 mg. Não é recomendada a utilização em doentes com compromisso hepático grave (Child-Pugh C).Não são necessários ajustes posológicos: doentes com compromisso hepático ligeiro; doentes com compromisso renal ligeiro ou moderado; com base no sexo; com base na etnia. Stivarga é para utilização por via oral e deve ser tomado à mesma hora todos os dias. Os comprimidos devem ser engolidos inteiros com água após uma refeição ligeira contendo menos de 30% de gordura. Contraindicações: Hipersensibilidade à substância ativa ou a qualquer um dos excipientes. Advertências e precauções especiais de utilização: Efeitos hepáticos: Recomenda-se que sejam realizados testes da função hepática; Doentes com síndrome de Gilbert; Doentes com compromisso hepático ligeiro ou moderado, Hemorragia; Isquemia cardíaca e enfarte do miocárdio; Síndrome de encefalopatia posterior reversível (SEPR); Perfuração e fístula gastrointestinais; Hipertensão arterial; Complicações da cicatrização de ferida; Toxicidade dermatológica; Anomalias dos testes laboratoriais bioquímicos e metabólicos. Em casos de agravamento de eventos de infecção deve considerar-se a interrupção do tratamento de Stivarga. Recomenda-se a interrupção de Stivarga em doentes que desenvolvam perfuração ou fístula gastrointestinal. Interações medicamentosas: Inibidores do CYP3A4 e UGT1A9 / indutores do CYP3A; Substratos da UGT1A1 e da UGT1A9; Substratos da Proteína de Resistência do Cancro da Mama (Breast Cancer Resistance Protein - BCRP) e da glicoproteína-P; Inibidores da glicoproteína-P e da BCRP/Indutores da glicoproteína_P e da BCRP; Substratos seletivos de isoformas CYP; Antibióticos; Agentes sequestrantes dos sais biliares. Efeitos indesejáveis: Infeção; Trombocitopenia; Anemia; Diminuição do apetite e da ingestão de alimentos; Cefaleias; Hemorragia; Hipertensão; Disfonia; Diarreia; Estomatite; Vómitos; Naúseas; Hiperbilirrubinemia; Reação cutânea mão-pé; Erupção cutânea; Alopecia; Astenia/Fadiga; Dor; Febre; Inflamação das mucosas; Perda de peso; Leucopenia; Hipotiroidismo; Hipocaliemia; Hipofosfatemia; Hipocalcemia; Hiponatremia; Hipomagnesemia; Hiperuricemia; Tremores; Neuropatia periférica; Perturbações do paladar; Boca seca; Refluxo gastroesofágico; Gastroenterite; Aumento das transaminases; Pele seca; Erupção cutânea esfoliativa; Espasmos musculares; Proteinúria; Aumento da amílase; Aumento da lípase; Razão normalizada internacional anormal; Reação de hipersensibilidade; Enfarte do miocárdio; Isquemia do miocárdio; Crise hipertensiva; Perfuração gastrointestinal; Fístula gastrointestinal; Pancreatite, Lesão hepática grave; Afeção ungueal; Eritema multiforme; Queratoacantoma/ Carcinoma de células escamosas da pele; Síndrome de encefalopatia posterior reversível (SEPR), Síndrome Stevens-Johnson, Necrólise epidérmica tóxica. Número da A.I.M.: 5579479. Data de revisão do texto: 08/2018. Medicamento sujeito a receita médica restrita, de utilização reservada a certos meios especializados. Para mais informações, deverá contatar o Titular da Autorização de Introdução no Mercado. Notifique acontecimentos adversos a: INFARMED (farmacovigilancia@infarmed.pt), Bayer Portugal (medical@bayer.com). Bayer Portugal, Lda. Rua Quinta do Pinheiro 5, 2794-003 Carnaxide. NIF: 500043256

1. STIVARGA (regorafenib) summary of product characteristics [global prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals. 2. Grothey A, Van Cutsem E, Sobrero A, et al; for the CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-312. 3. Li J, Qin S, Xu R, et al; on behalf of the CONCUR Investigators. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015;16(6):619-629. 4. Bendell J, Ciardiello F, Tabernero J, et al. Efficacy and safety results from IMblaze370, a randomised phase III study comparing atezolizumab + cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer. PowerPoint Presented at: European Society for Medical Oncology (ESMO) 20th World Congress on Gastrointestinal Cancer; June 20-23, 2018; Barcelona, Spain. 5. Ducreux M, Petersen LN, Öhler L, et al; on behalf of the CORRELATE Investigators. Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice: final analysis from the prospective, observational CORRELATE study. Presented at: European Society for Medical Oncology (ESMO) 20th World Congress on Gastrointestinal Cancer; June 20-23, 2018; Barcelona, Spain. Poster O-012. 6. Adenis A, de la Fouchardière C, Paule B, et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer. 2016;16:412. 7. Van Cutsem E, Martinelli E, Cascinu S. et al. Regorafenib for Patients with Metastatic Colorectal Cancer Who Progressed After Standard Therapy: Results of the Large, Single-Arm, Open-Label Phase IIIb CONSIGN Study. The Oncologist. 2018;23:1-8. 8. Bekaii-Saab TS, Ou F-S, Anderson DM, et al. Regorafenib dose optimization study (ReDOS): randomized phase II trial to evaluate dosing strategies for regorafenib in refractory metastatic colorectal cancer (mCRC) - an ACCRU Network study. Poster presented at: American Society of Clinical Oncology (ASCO) 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA. 9. Komatsu Y, Muro K, Yamaguchi K, et al. Safety and efficacy of regorafenib post-marketing surveillance (PMS) in Japanese patients with metastatic colorectal cancer (mCRC). J Clin Oncol. 2017;35(suppl):abstract 721-721. American Society of Clinical Oncology (ASCO) 2017 Gastrointestinal Cancers Symposium; June 2-6, 2018; Chicago, Illinois. Abstract 721. 10. Kopeckova K, Chloupkova R, Melichar B, et al. Regorafenib for metastatic colorectal carcinoma: a registry based analysis. Poster presented at: European Society for Medical Oncology (ESMO) 18th World Congress on Gastrointestinal Cancer; October 19-23, 2018; Munich, Germany. Abstract 468P. 11. Kudo T, Kato T, Kagawa Y, et al. Phase II dose titration study of regorafenib for patients with unresectable metastatic colorectal cancer that progressed after standard chemotherapy. Poster presented at: American Society of Clinical Oncology (ASCO) 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA. Abstract 821. 12. Schulz H, Janssen J, Strauss UP, et al. Clinical efficacy and safety of regorafenib (REG) in the treatment of metastatic colorectal cancer (mCRC) in daily practice in Germany: Final results of the prospective multicentre non-interventional RECORA study. Poster presented at: American Society of Clinical Oncology (ASCO) 2018 Gastrointestinal Cancers Symposium; January 18-20, 2018; San Francisco, CA.

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1

TRK FUSION PROTEINS ARE A PRIMARY ONCOGENIC DRIVER ACROSS MULTIPLE TUMORS IN ADULTS AND CHILDREN1,2

LOOK BELOW THE SURFACE TO FIND OUT WHAT’S DRIVING THE TUMOR

THERE’S MORE TO SOME CANCERS THAN MEETS THE EYE

LEARN MORE ABOUT TRK FUSION CANCER AT TRKCANCER.COM

Bayer AG51368 Leverkusen Germany

References: 1. Okimoto RA, Bivona TG. Tracking down response and resistance to TRK inhibitors. Cancer Discov. 2016;6(1):14-16. 2. Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34.

TRK, tropomyosin receptor kinase.

PP-VIT-PT-0001-1