Download Targeted Therapy

Is targeted therapy the future of
personalized cancer care?
Vibeke Kruse MD PhD
Medical Oncologist
Clinical Pharmacologist
Department of Medical Oncology
UZ Gent
22 November 2016
Outline
1) Introduction
2) Systemic therapy in oncology
• Chemotherapy
• Targeted Therapy
• Immunotherapy
3) Conclusions
Vibeke Kruse 2016
Outline
1) Introduction
2) Systemic therapy in oncology
• Chemotherapy
• Targeted Therapy
• Immunotherapy
3) Conclusions
Vibeke Kruse 2016
Personalized medicine
Breast Cancer – an example:
Breast cancer is NOT one disease
Vibeke Kruse 2016
Personalized medicine
Diagnosis of breast cancer:
 Primary tumor
 Lymph node involvement
 Metastatic disease
TNM classification – stage I-IV
Breast cancer is NOT one disease
Vibeke Kruse 2016
Personalized medicine
Diagnosis of breast cancer:
 Primary tumor
 Lymph node involvement
 Metastatic disease
 Surgery possible?
 Systemic treatment ?
 Chemotherapy ?
 Targeted therapy ?
 Radiotherapy ?
TNM classification – stage I-IV
Breast cancer is NOT one disease
Vibeke Kruse 2016
Personalized medicine
Treatment of breast cancer:
 Surgery
 Radiotherapy
 Systemic treatment
 Chemotherapy
 Targeted therapy
- Hormonal Treatment
- anti-HER2 treatment
- anti-VEGF treatment
Vibeke Kruse 2016
Personalized medicine
Treatment of breast cancer:
 Pathology report
• Size
• Differentiation
• Ki67%
 Surgery possible?
• Estrogen receptors
 Systemic treatment ?
• Progesteron receptor
 Chemotherapy ?
 Targeted therapy ?
 Radiotherapy ?
• HER2
 Staging (metastases ?)
 Patient
• Age
• Medical history
• Personal Whishes
• …
 Reimbursement
Vibeke Kruse 2016
Vibeke Kruse 2016
Outline
1) Introduction
2) Systemic therapy in oncology
• Chemotherapy
• Targeted Therapy
• Immunotherapy
3) Conclusions
Vibeke Kruse 2016
Systemic therapy
Chemotherapy
Targeted therapy
Immunotherapy
Vibeke Kruse 2016
Systemic therapy
Chemotherapy
Targeted therapy
Immunotherapy
Vibeke Kruse 2016
Chemotherapy
Mechanism of action

Not tumour specific

Inhibits cell division by targeting
different phases of the cell cycle

Can’t differentiate between
healthy and cancer cells

Attacks all rapidly dividing cells
-Bone marrow
-Digestive tract
-Hair follicles
-...
Chemotherapy
Vibeke Kruse 2016
Chemotherapy
Side effects:
Chemotherapy








Nausea
Changed taste
Aloplecia
Myelosuppression
Stomatitis
Increased risk for infection
Hand foot syndrome
….
Vibeke Kruse 2016
Chemotherapy
Treatment of side effects:
Vibeke Kruse 2016
Systemic therapy
Chemotherapy
Targeted therapy
Immunotherapy
Vibeke Kruse 2016
Targeted therapy
Vibeke Kruse 2016
Targeted therapy
We need: target + (available) treatment
Vibeke Kruse 2016
Targeted therapy
Same target – different organ
Vibeke Kruse 2016
Targeted therapy
Same target – different organ
HER2
10-15%
15-20%
Vibeke Kruse 2016
Targeted therapy
Same target – different
organ
HER2
Vibeke Kruse 2016
Targeted therapy
Same target – different organ
Vibeke Kruse 2016
Targeted therapy
Same target – different organ
BRAFmutation
50%
5-10%
Vibeke Kruse 2016
Targeted therapy
BRAF mutation melanoma
Flaherty NEJM 2010
Vibeke Kruse 2016
Targeted therapy
BRAF mutation Coloncarcinoma
Kopetz S et al. JCO.2015.
Vibeke Kruse 2016
Targeted therapy
The value of a target depends on the localisation of the
tumor
Vibeke Kruse 2016
Targeted therapy
Side effects:
Vibeke Kruse 2016
Systemic therapy
Chemotherapy
Targeted therapy
Immunotherapy
Vibeke Kruse 2016
Systemic therapy
Vibeke Kruse 2016
Checkpoint Blockade and Cancer
• CTLA-4–blocking antibodies release an
immune checkpoint at the activation step of
an immune response to cancer
• PD-1–blocking antibodies release an
immune checkpoint at the effector step of
an immune response to cancer
• Pembrolizumab is a PD-1–blocking antibody
with robust efficacy and manageable toxicity
in patients with advanced melanoma1-5
Reprinted with permission from Ribas A. N Engl J Med 2012;366:2517-9.
Copyright © 2012 Massachusetts Medical Society.
Human IgG4
KD: ~29 pM
PD-L1 IC50: ~0.1-0.3 nM
PD-L2 IC50: ~0.5-0.9 nM
1. Hamid O et al. N Engl J Med. 2013;392:134-144; 2. Robert C et al. Lancet. 2014;384:1109-1117; 3. Daud A et al. Presented at: Society
for Melanoma Research
2014 Annual Meeting; November 13-16, 2014; Zurich, Switzerland; 4. Robert C et al. Abstract LBA34. Presented at: ESMO 2014
Congress; September 26-30, 2014; Madrid, Spain; 5. Ribas A et al. Presented at: Society for Melanoma Research 2014 Annual Meeting;
November 13-16, 2014; Zurich, Switzerland.
Non-Conventional Response and I-O Therapy
Apparent progression upon radiographic imaging after initial I-O therapy can actually be a sign
of non-conventional response to I-O therapy. This response may occur when T cells infiltrate
1,2
the tumor site and cause tumors to flare or appearance of new lesions upon imaging.
I-O therapy
Tumor cells
T cells
infiltrating the
tumor site
Appearance of new
lesions upon imaging
I-O, immuno-oncology.
1. Wolchok JD et al. Clin Cancer Res. 2009;15:7412-7420.
2. Ribas A et al. Clin Cancer Res. 2009;15:7116-7118.
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Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions affect certain organ systems1
1.
2.
3.
4.
5.
Nervous system2
Eyes1,3
Skin1,2,4
Respiratory system1,2
Liver2,4
Endocrine system2,4
Gastrointestinal tract1-4
Hematopoietic cells5
Amos SM et al. Blood. 2011;118(3):499-509.
Chow LQ. Am Soc Clin Oncol Educ Book. 2013:280-285.
Robinson MR et al. J Immunother. 2004;27(6):478-479.
Phan GQ et al. Proc Natl Acad Sci U S A. 2003;100(14):8372-8377.
Lin TS et al. J Clin Oncol. 2010;28(29):4500-4506.
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irAE – prognostic value?
• Is there a link between response to immunotherapy and
development of an irAE?
• Some data support
an association
between clinical
benefit and the
induction of a
cutanous irAEs
Freeman-Keller et al. Clin Cancer Res; 22(4) February 15, 2016
Vibeke Kruse 2016
Vibeke Kruse 2016
ION | key assets in Ghent
growing base of preclinical and translational research
activity in cancer immunology
Bioscience Engineering
Statistics and Bioinformatics
VIB Biochemistry
Nanobody lab
Nuclear receptor lab
Cytokine receptor lab
Molecular immunology
Pharmaceutical Sciences
biopharmaceutical technology unit
Medicine and Health Sciences
Immunology – Hematology
Experimental Immunology
Dermatology Research Unit
Thoracic Tumor Immunology lab
Gastroenterology-Hepatology
Radiation Oncology
Lab of Experimental Cancer Research
VIB Inflamm. Research Center
Molecular & cellular oncology
Molecular signalling and cell death
Inflammation and immunity
Veterinary Science
Laboratory of gene therapy
KV Mar 2016
LABS
CLINICS
patients
Bioscience
Engineering
VIB-UGent
biomarker discovery
UZ Gent immuno-assays
translational
research
Veterinary
Sciences
• tumor
boards
• biobanks
IO in clinical trials
& routine practice
immuno-profiling
immuno-monitoring
Pharmaceutic
al Sciences
KV Mar 2016
The ION-Ghent steering group
Vibeke Kruse, Medical Oncology
Lieve Brochez, Dermatologic Oncology
Tessa Kerre, Hematological Oncology & Immunology
Katrien De Wolf, Piet Ost, Radiation Oncology
Karim Vermaelen, Thoracic Oncol. & Immunology
with support from Sofie Bekaert (BIMETRA) Pieter Rondou (CRIG)
KV Mar 2016
Outline
1) Introduction
2) Systemic therapy in oncology
• Chemotherapy
• Targeted Therapy
• Immunotherapy
3) Conclusions
Vibeke Kruse 2016
Conclusion
Is targeted therapy the future of
personalized cancer care?
 Targeted therapy is a cornerstone of cancer care
 But ….
•
Personalized cancer care is MORE than
targeted therapy alone
Not all cancers have a target (so far)
We need to define more targets and develop new targeted
therapies/making existing therapies available
•
•
•
Immunotherapy is of growing importance (target(s): different
aspects of the immune system)
Chemotherapy still plays an important role
High need for biomarkers
Vibeke Kruse 2016
Conclusion
Is targeted therapy the future of
personalized cancer care?
Vibeke Kruse 2016
Conclusion
Is targeted therapy the future of
personalized cancer care?
A combination of
 Chemotherapy
 Targeted therapy
 Immunotherapy
 Surgery
 Radiotherapy
 Combinations
 …..
Vibeke Kruse 2016
THANK YOU FOR YOUR
ATTENTION
[email protected]
Vibeke Kruse 2016