10,30 - 13,15

III Sessione“I risultati clinici”

Moderatori:

Michele Maio - Valter Torri

12,15 - 12,30

Rene e vescica

Giuseppe Procopio

Rene e prostata

GiuseppeProcopio

ImmunotherapyhastraditionallyplayedaroleinmRCC

1. McDermott D, et al. Cancer 2009;115(Suppl. 10):2298‒2305

2. Fyfe G. et al. J Clin Oncol.1995;13:688‒696

CytokinetherapyinmRCC

§ TreatmentwithIFN-α andIL-2

havebothshownclinicalactivity

inmRCC1

§ DurableresponsestoIL-2(ORR:14%

with5%CRand9%PR)butassociated

withsubstantialtoxicity2

Responsedurationinall responderstoIL-2treatment

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.00 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

MonthsPe

rcen

t in

res

pons

e

Complete responsePartial response

FDAapproval in1992

Randomized DoseRanging SingleAgent Nivolumab inRCC(n=168)

Motzer RJ et al, J Clin Oncol 2015 May 1;33(13): 1430-7

Dose 0.3mg/kg 2mg/kg 10mg/kgIVq3wN=60

IVq3wN=54

IVq3wN=54

PriorRx 70%>2priortherapiesNoRxnaivepts

ORR(%) 20% 22% 20%mPFSPrimaryendpoint

2.7mo 4.0mo 4.2mo

mOS 18.2 25.5 24.7G3/4Tox 5% 17% 13%

Esempiodiapoconimmagineedidascalia- 1

Studydesign

§ Primaryendpoint§ Overallsurvival(OS)

§ Secondaryendpointsincluded§ Objectiveresponserate(ORR)§ Progression-freesurvival(PFS)§ Adverseevents§ Qualityoflife(QoL)§ OSbyPD-L1expression

Studyendpoints

Demographicsandbaselinecharacteristics

Overallsurvival

Overallsurvivalbysubgroupanalyses

OverallsurvivalbyPD-L1expression

Antitumoractivity

Progression-freesurvival

SafetySummary

Treatment-relatedAesin≥10%ofpatients

ChangefrombaselineinqualityoflifescoresonFKSI-DRS

Studion-going

Algoritmopotenziale

LINEESUCCESSIVE

§ Nivolumabèilprimoagenteingradodiaumentarel’OSnelmRCCpost-TKI

§ Nivolumabpracticechanging

§ Favorevoleprofiloditollerabilità

§ PD-L1statusprognosticomanonpredittivodirisposta

§ Ongoingstudidiimmunoterapiainprimalinea(Atezolizumab+bevacizumab,

Nivolumab+ipilimumab)

Conclusioni

Timeline for systemic therapy development inurothelial cancer

Vogelzang N,ASCO 2015

Atezolizumab (MPDL3280A)inUBC

Petrylak DP, ASCO2015

ORR:34%(30/87)

IMvigor210:PFSandOS

IMvigor210:efficacybysubgroupanalysis

IMvigor210:cohort2

Pembrolizumab (MK-3475)inUBC

ORR: 27.6% (8/29)

Plimack ER, ASCO 2015

Hahn NM, ASCO 2015

Challenges in 2nd line bladder

Presented By Peter Albers at 2015 ASCO Annual Meeting

Summary on PD-1 and PDL-1 inhibition in 2nd line bladder cancer

Presented By Peter Albers at 2015 ASCO Annual Meeting

Comparison PD-1/PDL-1 inhibition to Eribulin in 2nd line bladder cancer

Presented By Peter Albers at 2015 ASCO Annual Meeting

Fase Target Farmaco Comparator Linea EndPointII

PD-L1Atezolizumab

Nessuno2

ORRIII CHT PFSIII MEDI4736* CHT 1 PFSII

PD-1Nivolumab Nessuno 2 PFS

III Pembrolizumab CHT 2 PFSII CTLA-4 Ipilimumab** Nessuno 1 1-yOS

*± Tramelimumab

**+Cisplatino-Gemcitabina

ONGOING TRIALS WITH IMMUNOTHERAPIES

Checkpoint Clinical trials in Bladder Cancer

Apolo AB,GU-ASCO2015

GUTeamINT