Post on 25-Dec-2014
description
Conclusiones: de Sydney a Denver
Sefa Terrasa Pons Oncología Médica
Hospital Universitario Son Espases Palma de Mallorca
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
Crizotinib
(n=173)
Chemotherapy
(n=174)
Events, n (%) 100 (58) 127 (73)
Median, mo 7.7 3.0
HR (95% CI) 0.49 (0.37 to 0.64)
P <0.0001
Crizotinib vs Chemotherapy in ALK +
NSCLC P
rob
ab
ilit
y o
f su
rviv
al
wit
ho
ut
pro
gre
ss
ion
(%
)
100
80
60
40
20
0
0 5 10 15 20 25
Time (months)
173 93 38 11 2 0
174 49 15 4 1 0
No. at risk
Crizotinib
Chemotherapy
Shaw et al., NEJM 2012
Estrategia global: • Aunar esfuerzos de todos los profesionales
implicados ( investigadores básicos, clínicos, estadistas, informáticos…), de la industria farmacéutica, de las instituciones, delas asociaciones (IASLC) …
Magnitude of Genomic Derangement is greatest in Lung Cancer
From The Cancer Genome Atlas Project: Govindan R. J Clin Oncol. 2012 (Proc ASCO Annual Meeting);30 (suppl): abstr 7006.
1 / Mb
10 / Mb
100 / Mb
0.1 / Mb
81 64 38 316 100 17 82 28 n=109 119 21 40 20
Hematologic & Childhood Cancers
Carcinogen-induced Cancers
??
Ad
en
oca
Squ
amo
us
Ovarian, Breast, Prostate Cancers
Mutations Per Mb DNA
Drugable targets in smokers and never smokers
Govindan et al, 2012 Cell 150: 1121
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
CT*
TT=Targeted therapy, CT=chemotherapy (docetaxel or gemcitabine), E=erlotinib
MASTER PROTOCOL (FOCR): Squamous Lung Cancer- 2nd Line Therapy
Biomarker C
TT C+CT CT*
Endpoint
(Interim PFS)
OS
Biomarker Β
TT B CT*
Endpoint
(Interim PFS)
OS
Biomarker A
TT A CT*
Endpoint
(Interim PFS)
OS
Biomarker Profiling (NGS/CLIA)
Biomarker D
TT D+E E*
Endpoint
(Interim PFS)
OS
Non-Match Drug
Biomarker Non-Match
PI: V. Papadimitrakopoulou (SWOG)
Multiple Phase II- III Arms with “rolling Opening & Closure
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?
Gracias
josefa.terrasa@ssib.es