Cáncer de Vejiga – Cara a cara: • A favor de la Inmunooncología

Josep M Piulats

L Galluzzi et al. Oncotarget 5, 12472-12508 (2014)

L Galluzzi et al. Oncotarget 5, 12472-12508 (2014)

Anti-PD1 Anti-PDL1 Anti-CTLA4

L Galluzzi et al. Oncotarget 5, 12472-12508 (2014)

Anti-PD1 Anti-PDL1 Anti-CTLA4

Chemotherapy

Immunogenic Cell Death (ICD):

Immunogenic Cell Death (ICD):

Plasma membrane characteristics

Inflammatory cytokines released from dying cells

End-stage degradation products with pro-

inflammatory properties

TP53 activation and immunological consequences

O Kepp et al. Oncoimmunol 3, e955691 (2014)

O Kepp et al. Oncoimmunol 3, e955691 (2014)

Platinum salts as an ICD inductor:

SV Hato et al. Clin Cancer Res 20, 2831-2837 (2014)

Platinum salts as an ICD inductor:

SV Hato et al. Clin Cancer Res 20, 2831-2837 (2014)

Is bladder cancer an immunogenic disease?:

MS Lawrence et al. Nature 499, 214-218 (2013)

Is bladder cancer an immunogenic disease?:

A Snyder et al. NEJM 371, 2189-2199 (2014)

NA Rizvi et al. Science 348, 124-128 (2015)

JE Rosenberg et al. Lancet 387, 1909-19-20 (2016)

Is bladder cancer an immunogenic disease?:

Is bladder cancer an immunogenic disease?:

CY Ock et al. Clin Cancer Res 22, 2261-2270 (2016)

- Chemotherapy can be considered immunotherapy. - Bladder cancer has high rate of neoantigens. - Bladder cancer show a 30% of tumors with high CD8/PDL1.

What about clinical efficacy???

Atezolizumab:

JE Rosenberg et al. Lancet 387, 1909-19-20 (2016)

Pembrolizumab:

J Bellmunt et al. New Engl J Med 376, 1015-1026 (2017)

Pembrolizumab:

J Bellmunt et al. New Engl J Med 376, 1015-1026 (2017)

Something +

Synergy is the interaction of two or more agents or forces so their

combined effect is greater than the sum of their individual effects.

Sequential or Concomitant treatments.

DRUG A

DRUG B

DRUG A

DRUG B

Rational or Empirical combinations. Empirical combinations use one

drug that is standard treatment for that disease; Rational combinations try

to combine drugs with the objective to maximize any synergistic effect.

- Chemotherapy can be considered immunotherapy. - Bladder cancer has high rate of neoantigens. - Bladder cancer show a 30% of tumors with high CD8/PDL1.

What about clinical efficacy???

- Anti-PD1 antibodies are the standard of treatment in second line. - Rational combination with chemotherapy is being explored in

first line treatment.