I nuovi farmaci per il trattamento del melanoma

I nuovi farmaci per il
trattamento del melanoma
Pisa, 24 aprile 2012
Antonella Romanini
[email protected]
Curve di sopravvivenza
1.0
0.9
Stage I (n=9175)
Proportion Surviving
0.8
0.7
85%
0.6
Stage II (n=5739)
0.5
0.4
Stage III (n=1528)
7%
0.3
0.2
Stage IV (n=1158)
0.1
8%
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Survival, years
Reproduced with permission from Balch CM, Buzaid AC, Soong SJ, et al. J Clin Oncol. 2001;19:3635-3648.
Images courtesy of Kenneth Tanabe, MD
MELANOMA AL
VIDEODERMATOSCOPIO
La Diagnosi di melanoma è solo
istologica
Curve di sopravvivenza
1.0
0.9
Stage I (n=9175)
Proportion Surviving
0.8
0.7
85%
0.6
Stage II (n=5739)
0.5
0.4
Stage III (n=1528)
7%
0.3
0.2
Stage IV (n=1158)
0.1
8%
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Survival, years
Reproduced with permission from Balch CM, Buzaid AC, Soong SJ, et al. J Clin Oncol. 2001;19:3635-3648.
SLN
“Medicine is a science of
uncertainty and an art of probability”
Sir William Osler
Forest plot of hazard ratios (HRs) (interferon alpha
[IFN-a] vs control) for disease-free survival
HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001
18%
J Natl Cancer Inst 2010;102:493–501
Forest plot of hazard ratios (HRs) (interferon alpha
[IFN-a] vs control) for overall survival
HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002
11%
J Natl Cancer Inst 2010;102:493–501
Curve di sopravvivenza
1.0
0.9
Stage I (n=9175)
Proportion Surviving
0.8
0.7
85%
0.6
Stage II (n=5739)
0.5
0.4
Stage III (n=1528)
7%
0.3
0.2
Stage IV (n=1158)
0.1
8%
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Survival, years
Reproduced with permission from Balch CM, Buzaid AC, Soong SJ, et al. J Clin Oncol. 2001;19:3635-3648.
RR
Compaison of
response rate and
overall survival in
metastatic melanoma
OS
Eigentler TK et al.
Lancet Oncol 2003; 4: 748–59
Summary of The Desired
T-cell Response to Tumours
APC
T-cells
T-cell
1 - T-cell activation
2 - T-cell proliferation
T-cells
T-cells
Tumour
3 - Infiltration of tumour site
Destroyed tumour cells
4 - Tumour cell destruction
However – tumours have the ability to evade the immune system, and
T-cell activation is under regulatory control. Immunotherapeutic
strategies aim to enhance this natural response
19
Overview of immunoediting
Autoimmunity Correlates With Tumor Regression in
Patients With Metastatic Melanoma Treated With Anti–
Cytotoxic T-Lymphocyte Antigen-4
Peter Attia, Giao Q. Phan, Ajay V. Maker, Michael R. Robinson, Martha M. Quezado, James C. Yang,
Richard M. Sherry, Suzanne L. Topalian, Udai S. Kammula, Richard E. Royal, Nicholas P. Restifo,
Leah R. Haworth, Catherine Levy, Sharon A. Mavroukakis, Geoff Nichol, Michael J. Yellin,
and Steven A. Rosenberg
J Clin Oncol 23:6043-6053. 2005
J Natl Cancer Inst 2010;102:1388–1397
Condizioni biopatologiche caratterizzate da
specifici profili biomolecolari
Curtin et al. NEJM, 2005
Representative PET scans for patients taken pre-dose
and following 2 weeks of dosing with PLX4032.
G Bollag et al. Nature 467, 596-599 (2010) doi:10.1038/nature09454
Note: This figure is from a near-final version AOP and may change prior to final publication in print/online
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