molecular tumor board in oncology · 2019-04-24 · pd após docetaxel, cabazitaxel, abiraterona,...
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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
