Molecular Tumor Board in Oncology

Diogo Assed Bastos, MDGenitourinary OncologyHospital Sirio-Libanês

Instituto do Cancer do Estado de São Paulo

Personalized MedicineApplication of patient-specific profiles, incorporating genetic and genomic data as well as clinical and environmental factors, to assess individual risks and tailor prevention and disease-management strategies.

Make no mistake: we have been using “personalized medicine” for many years

Ex: 68 yo male with localized prostate cancer, PSA of 15ng/mL, cT2, Gleason 7. Comorbidities: HTN, DM, heart failure, prior stroke.

Options:

-Active surveillance

-Radical Prostatectomy

-External beam radiation therapy ± ADT

-Brachytherapy

Personalized Medicine

Make no mistake: we have been using “personalized medicine” for many years

Ex: 68 yo male with localized prostate cancer, PSA of 15ng/mL, cT2, Gleason 7. Comorbidities: HTN, DM, heart failure, prior stroke.

Options:

-Active surveillance

-Radical Prostatectomy

-External beam radiation therapy ± ADT

-Brachytherapy

Molecular test: ONCOTYPE Dx®

- Low risk

Personalized Medicine

Applications in cancerBefore: one-dose-fits-

all approachAfter: personalized medicine (from genotype to phenotype)

Genotype A B C D

Phenotype Histology, KPS

Histology, KPS

Histology, KPS

Histology, KPS

Treatment “A" Treatment “A"

Treatment “B"

Treatment “C"

Treatment “D"

Personalized Medicine in OncologyDisease Molecular Target Drug

CML BCR-ABL Imatinib

Breast HER-2 Trastuzumab

GIST KIT Imatinib

Lung EGFR Erlotinib, Gefitnib

Lung ALK Crizotinib

Head and neck EGFR Cetuximab

Colorectal EGFR Cetuximab, Panitumumab

Gastric HER-2 Trastuzumab

Melanoma BRAF Vemurafenib

Renal cell VEGF Sunitinib, Pazopanib

Renal cell mTOR Everolimus, Temsirolimus

Prostate cancer AR Abiraterone, enzamutamide

Garraway L. J Clin Oncol, 2013

Actionable genomic alterations in solid tumors

Challenges

Personalized Medicine: Challenges

Access / Cost: test, drug, clinical trial

Rapidly evolving knowledge / technology

Tumor heterogeneity

High number of genomic alterations, not all with

matched targeted therapy

Components of a genomics-driven cancer medicine

Garraway L. J Clin Oncol, 2013

Molecular Tumor Board

Genomic-based true multidisciplinary meeting

Goal: Discuss cases with genomic alterations

Implications of specific genomic alterations

Potential for prevention and germline testing

Somatic alterations: match with best available treatment (on

label, off label, clinical trials) to maximize outcomes

Molecular Tumor Board

Annals of Oncology 28: 3070–3075, 2017

Molecular Tumor Board

Examples

Annals of Oncology 28: 3070–3075, 2017

47 anos, sem comorbidadesAF: sem antecedentes familiares de câncer

•04/01/2013: PSA 10,20•07/05/2013: PSA 11,60 biópsia: adenocarcinoma Gleason 3+3(6).

•08/10/2013 - Prostatectomia aberta. AP: adenocarcinoma de próstataGleason 4+4 (8) bilateral com extensão extra-capsular e invasão de VVSSbilateralmente, 3/15 LNs comprometidos. pT3bN1Mx.

– ADT iniciada em dez/2013– Abril-março/2014: RT adjuvante (69Gy)

•04/2015: Progressão óssea e linfonodal (mCRPC)– PD após Docetaxel, Cabazitaxel, Abiraterona, Enzalutamida

• 12/01/18:– ECOG 2-3– Hepatomegalia dolorosa– Dor não controlada– Progressão de doença pleural, linfonodal, hepática, óssea

• Internação Hospitalar – suporte e discussão deconduta

s/p Abiraterona

20/11/17

s/p Cabazitaxel x2

02/01/18

10/01/18

PSA: 197 PSA 478,459 PSA 917,7

Foundation One

2014: alteração do padrão miccional – noctúria e polaciúria.

08.2014: PSA 40,3.

08.2014 – Biópsia prostática. AP: Adenocarcinoma acinar usual Gleason 9 (4+5) em 5 fragmentos e Gleason 8 em dois fragmentos.

10.2014 – Prostatectomia Radical. - Adenocarcinoma Gleason 10 (5+5) com áreas extensas de padrão ductal, pT3b pN1 (4/12 LNs)

12.2014 – PSA 2,1.01.2015 – PSA 5,8.01.2015 – PET colina: hipercaptação em múltiplas linfonodomegalias

pélvicas e LN paraórtico.

62 anos, sexo masculino, ECOG 0.

05.02.2015 – ADT com Gosserelina PSA 0,029 em 11.09.2015

06.01.2016 – PSA 0,43 10.03.2016 – PSA 0,8609.04.2016 – PSA 1,80 Início de ABIRATERONA + Prednisona.

09.2016 – PSA 0,03605.2018 – PSA 0,4808.2018 – PSA 4,509.2018 – PSA 6,3

62 anos, sexo masculino, ECOG 0.

MAF:- CDK12 K837fs*20 = 8.2%- CDK12 K509fs*103 = 16.8%- FANCA F1263del = 35.2%

INVITAE germline: VUS em NTHL1

62 anos, sexo masculino, ECOG 0.

Incluído no Estudo Check-Mate 9kd

Conclusions

Growing significance of MTB as genomic multidisciplinary meeting

Several challenges to implement and develop

Importance for clinicians, geneticits and patients, especially in a scenario of increasing complexity

Obrigado!

04/04/2019

diogo.bastos@hsl.org.br