1. Conclusiones: de Sydney a Denver
Sefa Terrasa Pons
Oncología Médica
Hospital Universitario Son Espases
Palma de Mallorca
2. Conclusiones
• Las aportadas por cada uno de los
ponentes en cada uno de los temas.
De Sydney a Denver
• Del 2013 al 2015, futuro a corto plazo
• Presidente del IASLC del 2013 al 2015:
Toni Mok
3.
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21.
22.
23.
24.
25. Crizotinib vs Chemotherapy in ALK +
NSCLC
Probability of survival without
progression (%)
100
Crizotinib
(n=173)
(n=174)
100 (58)
127 (73)
7.7
Events, n (%)
80
Chemotherapy
3.0
Median, mo
0.49 (0.37 to 0.64)
HR (95% CI)
<0.0001
P
60
40
20
0
0
5
10
15
20
25
2
1
0
0
Time (months)
No. at risk
Crizotinib
Chemotherapy
173
174
93
49
38
15
11
4
Shaw et al., NEJM 2012
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35.
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38.
39. Estrategia global:
•
Aunar esfuerzos de todos los profesionales
implicados ( investigadores básicos, clínicos,
estadistas, informáticos…), de la industria
farmacéutica, de las instituciones, delas
asociaciones (IASLC) …
40.
41.
42.
43.
44. Magnitude of Genomic Derangement is greatest in Lung Cancer
n=109
81
64
38
316
100
17
82
28
119
Mutations
Per Mb DNA
40
Carcinogeninduced
Cancers
100 / Mb
Ovarian, Breast,
Prostate Cancers
1 / Mb
0.1 / Mb
??
From The Cancer Genome Atlas Project: Govindan R. J Clin Oncol. 2012 (Proc ASCO Annual Meeting);30 (suppl): abstr 7006.
Squamous
Hematologic &
Childhood Cancers
Adenoca
10 / Mb
21
20
45. Drugable targets in smokers and never smokers
Govindan et al, 2012 Cell 150: 1121
46.
47. Low Frequency Drivers: Challenges
• A separate trial for each drug or genotype population ?
• How relevant is prior treatment with chemo?
Chemonaive vs pretreated
• Do we always need a chemo (or placebo) comparator?
Which threshold of activity (RR, PFS) make this
unnecessary
• Are historical comparisons approppiate ?
Prospective phase II-III trials
48.
49.
50.
51.
52.
53. MASTER PROTOCOL (FOCR): Squamous Lung Cancer- 2nd Line Therapy
CT*
Biomarker
Profiling (NGS/CLIA)
Biomarker
Non-Match
NonMatch
Drug
Multiple Phase II- III Arms with “rolling Opening & Closure
Biomarker A
TT A
CT*
Endpoint
(Interim PFS)
OS
Biomarker Β
TT B
CT*
Endpoint
(Interim PFS)
OS
Biomarker C
TT C+CT
CT*
Endpoint
(Interim PFS)
OS
Biomarker D
TT D+E
E*
Endpoint
(Interim PFS)
OS
TT=Targeted therapy, CT=chemotherapy (docetaxel or gemcitabine), E=erlotinib
PI: V. Papadimitrakopoulou (SWOG)
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57. De Sydney a Denver
•
•
•
•
•
¿Podremos retrasar o prevenir la resistencia
a las terapias dirigidas?
Nuevas dianas tratables: ROS 1, KRAS,BRAF,
HER2,PIK3CA, MET
Posibles dianas en ca. Escamoso: FGFR1,
PIK3CA
Que papel tendrá la inmunoterapia
¿Combinaciones de tratamientos diana con
inmunoterapia?