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