APLICACIONES DE LA INMUNOTERAPIA · KEYNOTE-024: diseño del estudio de pembrolizumab frente a...

APLICACIONES DE LA INMUNOTERAPIA

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Histologic Subtypes

Wahbah M, et al. Ann Diagn Pathol. 2007;11:89-96.American Cancer Society database.

Decreasing Incidence of Squamous Cell Subtype Over Time

85% of lung cancers are NSCLC

Adenocarcinoma

Squamous cell carcinoma

Large cell carcinoma

Other or not otherwise specified

40%20%

10% to 15%

25% to 30%

Adenocarcinoma

Squamous cell

Large cell

45

40

35

30

25

20

15

10

5

0

Ca

nce

r In

cid

en

ce (

%)

Yr of Diagnosis (3-Yr Moving Average)

Localizado16%

LocamenteAanzado22%

Metastásico57%

NoConocido

5%

ESTADIOALDIAGNÓSTICO

4,5%

28,9%

55,6%

7,5%

0 10 20 30 40 50 60

Metastásico

LocalmenteAvanzado

Localizado

Noconocido

Supervivenciaa5años

LOCAL RESECABLECirugía +- QT

LOCAL RESECABLE AVANZADOQT neoadyuvante + tratamiento local

LOCAL NO RESECABLE RT + QT

METASTÁSICOS 1L

QuimioterapiaAntiangiogénicos *

2LQuimioterapia

TRATAMIENTO FUTURO INMUNOTERAPIA

INMUNOTERAPIA ADYUNATE

INMUNOTERAPIA NEOADYUVANTE

2019 INMUNOTERAPIA +- QT

2019 IO MANTENIMIENTORT+QT+IO

2015 INMUNOTERAPIA

1970 1980 1990 2000

Docetaxel2000

2010

Pemetrexed‡

2009

Median OS, months

12+~8–10

~6~2–4

13+

Carboplatin*1989

Gemcitabine1996

Vinorelbine1994

Bevacizumab‡

2006Paclitaxel1998

Cisplatin*1978

Despite advances, only small incrementalOS benefits in overall patient population

*Not approved in NSCLC, but commonly used; †Restricted to patients participating in a clinical trial or continuing to benefit from treatment already initiated; ‡Non-squamous NSCLC only; §ALK-positive NSCLC only; **EGFR exon 19 deletions or exon 21 (L858R) substitution mutations only;#Afatinib is approved for the treatment of patients with activating EGFR mutations but only PFS data have been published (May 2014).

U.S. Food and Drug Administration. Available at www.fda.gov. Accessed September 2014; European Medicines Agency. Available at

http://www.ema.europa.eu. Accessed September 2014; NCCN Guidelines. Non-small cell lung cancer. v3.2014.

Dr. Mark A. Socinski https://bit.ly/2Ld0jng

Mantenimiento

5-Y OS: 13.4% NIVO vs 2.6% DOC

Additional Exploratory Biomarkers Under Investigation for I-O Therapies1−12

Biomarker

investigations

TILs/

immunoscore

(eg, CD4 and

CD8 T cells)Gene expression

signatures

Other tumor immune

marker expression

(eg, CTLA-4, PD-L2)

Mutational load/burden,

neo-antigens

TCR

sequencing Other known oncogenic

driver mutations

(eg, EGFR, KRAS, BRAF)

Tumor

biomarkers Immune monitoring: absolute

lymphocyte count, circulating

T-cell subsets

Gene expression

profiling:

peripheral blood

TCR

sequencing

Serum chemokines/cytokines:

interferons, interferon

inducible factors, serum

soluble factors

sPD-L1

Circulating

miRNAsAntitumor

antibodies

SNPs

(germline)

Peripheral

biomarkers

1. Sosman JA et al. Poster presentation at ASCO 2013. TPS3114. 2. Choueiri TK et al. Oral presentation at ASCO 2015. 4500. 3. Clinical Protocol CA209009. 4. Lawrence MS et al. Nature. 2013;499(7457):214-218.5. Antonia SJ et al. Poster presentation at WCLC 2013. P2.11-035. 6. Weber JS et al. Lancet Oncol. 2015;16(4):375-384. 7. Brown SD et al. Genome Res. 2014;24(5):743-750. 8. Postow MA et al. J TranslMed. 2014;12(suppl 1):O8. 9. Komatsu N et al. Cancer. 2012;118(12):3208-3221. 10. Wang Z et al. Med Hypotheses. 2013;81(1):41-43. 11. Luborsky J et al. Am J Reprod Immunol. 2005;54(2):55-62. 12. Schneider BP et al. Lancet Oncol. 2012;13(10):e427-e436.

Importancia de la selección de pacientes porla expresión de PD-L1

ESTADIOS METATÁSICOSSEGUNDA LÍNEA TRAS DOBLETE DE PLATINO

ESTADIOS METATÁSICOSPRIMERA LÍNEA

KEYNOTE-024: diseño del estudio de pembrolizumab frente a quimioterapia

Reck M et al. N Engl J Med. 2016;375(14):1–11. TPS = puntuación de proporción tumoral

SLP superior con PEMBROLIZUMAB 200 mg Q3W frente a quimioterapia(HR 0,50, IC del 95%, 0,37–0,68; P<0,001) en pacientes con PD-L1 ≥50%

–Reducción del 50% del riesgo de progresión de la enfermedad o muerte con PEMBROLIZUMAB frente a quimioterapia

a Patients with a sensitizing EGFR mutation or ALK translocation must have disease progression or intolerance of treatment with one or more approved targeted therapies. b Atezolizumab: 1200 mg IV q3w. c Carboplatin: AUC 6 IV q3w. d Paclitaxel: 200 mg/m2 IV q3w. e Bevacizumab: 15 mg/kg IV q3w.

IMpower150 Study Design

Arm A

Atezolizumabb + Carboplatinc + Paclitaxeld

4 or 6 cycles

Atezolizumabb

Arm C (control)

Carboplatinc + Paclitaxeld

+ Bevacizumabe

4 or 6 cycles

Bevacizumabe

Surv

ival

fo

llow

-up

Stage IV or recurrent metastatic nonsquamous NSCLCChemotherapy-naivea

Tumor tissue available for biomarker testing

Any PD-L1 IHC status

Stratification factors:• Sex• PD-L1 IHC expression• Liver metastases

N = 1202

R1:1:1

Arm B

Atezolizumabb + Carboplatinc + Paclitaxeld

+ Bevacizumabe

4 or 6 cycles

Atezolizumabb

+ Bevacizumabe

Maintenance therapy(no crossover permitted)

Treated with atezolizumab until PD per RECIST v1.1

or loss of clinical benefit

AND/OR

Treated with bevacizumab until PD per RECIST v1.1

HRa, 0.78 (95% CI: 0.64, 0.96)

P = 0.0164Median follow-up: ~20 mo

a Stratified HR.Data cutoff: January 22, 2018

25

OS in the ITT-WT (Arm B vs Arm C)

• Statistically significant and clinically meaningful OS benefit with atezolizumab + bevacizumab + chemotherapy vs bevacizumab + chemotherapy was observed

Ove

rall

Surv

ival

(%

)

Time (months)

Median, 19.2 mo(95% CI: 17.0, 23.8)

Median, 14.7 mo(95% CI: 13.3, 16.9)

Landmark OS, %

Arm B:

atezo + bev +

CP

Arm C:

bev + CP

12-month 67% 61%

18-month 53% 41%

24-month 43% 34%

Dr. Mark A. Socinski https://bit.ly/2Ld0jng

ESTADIOS LOCALMENTE AVANZADODESPUÉS DE RADIOTERAPIA-QUIMIOTERAPIACONCOMITANTE

ESTADIO PRECOZNEOADYUVANCIA

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