Estado actual de terapia sistémica en cáncer renal metastásico

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YOUR LOGO Mauricio Lema Medina MD Clínica de oncología Astorga, Clínica SOMA, Medellín Estado actual del manejo sistémico Curso de urología oncológica de la Sociedad Colombiana de Urología, Bucaramanga, 05.11.2016

Transcript of Estado actual de terapia sistémica en cáncer renal metastásico

Page 1: Estado actual de terapia sistémica en cáncer renal metastásico

Mauricio Lema Medina MD

Clínica de oncología Astorga, Clínica SOMA, Medellín

Estado actual del manejo sistémico

Curso de urología oncológica de la Sociedad Colombiana de Urología, Bucaramanga, 05.11.2016

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Mauricio Lema: Conflicto de interés

Honorarios por conferencias (2016): BMS, Servier, Roche, Novartis, MSD, Aztra-Zeneca, AMGEN, PfizerGrant de investigación:GSK/Novartis

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@ONCONERD

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BHD=Birt-Hogg-Dubé; FH=fumarate hydratase; VHL=von Hippel-Lindau.Modified from Linehan WM et al. J Urol. 2003;170:2163-2172.

Histological Classificationof Human Renal Epithelial Neoplasms

RCC

Clear cell75%

Type

Incidence (%)

Associated mutations VHL

Papillary type 1

5%

c-Met

Papillary type 2

10%

FH

Chromophobe

5%

BHD

Oncocytoma

5%

BHD

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CJ Creighton et al. Nature 000, 1-7 (2013) doi:10.1038/nature12222

Somatic alterations in ccRCC.

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RCC Therapy: Targeting VEGF at Multiple Levels

AKT

mTOR HIFɑVHL

PI3K

Cell stimuli(eg, growth factors)

Cell growthsurvival

HIFɑHIFɑ

HIFɑ

Inactivated VHL tumor suppressor gene

Hypoxia

VEGF

PDGF

VEGFR

PDGFR

TemsirolimusEverolimus

SunitinibSorafenibPazopanib

AxitinibCabozantinib

Bevacizumab

HIFɑ

Adapted from Rini BI, et al. Lancet. In press.

Tumor

EndothelialCell

Cabozantinib

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Motzer RJ et al. J Clin Oncol. 2002;20:289-296.

MSKCC Risk Factor Model in mRCC

0 risk factors (n=80 patients)1 or 2 risk factors (n=269 patients)3, 4, or 5 risk factors (n=88 patients)

Risk factors associated with worse prognosis• KPS <80• Low serum hemoglobin (13 g/dL/11.5 g/dL: M/F) • High corrected calcium (10 mg/dL)• High LDH (300 U/L)• Time from Dx to IFN- <1 yr

Time From Start of IFN- (years)

Prop

ortio

n Su

rviv

ing

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 2 1614131195436 151210876

MS:20 mo10 mo4 mo

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Active Surveillance for Metastatic or Recurrent RCC: Retrospective Analysis

• 58 pts, 42 with recurrent RCC (n = 42) and 14 with initially metastatic RCC followed with active surveillance

• Karnofsky PS: 39 pts 100%, 14 pts 90%• 48 pts (83%) had SD as best response during active surveillance• Median follow-up: 31.4 mos• 47 (81%) pts had disease progression by cutoff date• After disease progression, 30 (52%) on systemic treatment:

sunitinib, pazopanib, 4 immunotherapy, 1 temsirolimus

Park I, et al. ASCO GU 2014. Abstract 426.

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Active Surveillance for RCC: TTP and OS

Park I, et al. ASCO GU 2014. Abstract 426.

Median OS: 91.1 mos (95% CI: 30.7-151.6)Median TTP: 12.4 mos (95% CI: 8.4-16.5)

Mos

• Pati

ents

Sur

vivi

ng (%

) 80

60

40

00 40 80 120 160

100

20

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Active Surveillance for RCC: Conclusions

• Predictors of short TTP (univariate analysis)– Liver metastasis (P = .011)– Karnofsky PS(P = .003)– Neutrophilia (P < .001)– Thrombocytosis (P = .011)– Time from diagnosis to active surveillance (P < .001)– Heng et al risk group (P < .001)

• Active surveillance may be viable treatment option in pts with asymptomatic or minimally symptomatic mRCC, particularly with good Karnofsky PS and no liver metastases

Park I, et al. ASCO GU 2014. Abstract 426.

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Phase III study of sunitinib vs IFN-αas first-line treatment of mRCC1,2

n=750

Primary endpointPFS

Secondary endpointsOSORRPatient-reported outcomesSafety

Eligibility criteria:

≥18 years of age

mRCC, with clear-cell histology

No previous systemic treatment

Measurable disease (RECIST)

ECOG performance status 0 or 1

Adequate organ function

RANDOMISATION

IFN-α (n=375)Week 1: 3 MIU SC 3 × weeklyWeek 2: 6 MIU SC 3 × weekly

From week 3: 9 MIU SC 3 × weekly

Sunitinib (n=375)50 mg/day (schedule 4/2)

1. Motzer et al. J Clin Oncol 2009;27:3584–90.2. Motzer et al. N Engl J Med 2007;356:115–24.

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Phase III study of sunitinib vs IFN-α:PFS (independent review)1,2

13

Number at riskSunitinib 375 140 156 54 10 1IFN-α 375 124 46 15 4 0

Time, months

PFS

prob

abili

ty

1.0

0.8

0.6

0.4

0.2

00 5 10 15 20 25

Median PFS (95% CI)Interim analysis (graph)Final analysis

Sunitinib 11.0 months (10.7–13.4)11 months (11–13)IFN-α 5.1 months (3.9–5.6) 5 months (4–6)

HR=0.54 HR=0.539(95% CI=0.44–0.66) (95% CI=0.451–0.643)

p<0.000001 p<0.001

1. Motzer et al. J Clin Oncol 2007;25(Suppl):Abstract 5024 (Presentation).2. Motzer et al. J Clin Oncol 2009;27:3584–90.

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Number of deaths/number at riskSunitinib 0/375 44/326 38/283 48/229 42/180 14/61 4/2 IFN-α 0/375 61/295 46/242 52/187 25/149 15/53 1/1

Phase III study of sunitinib vs IFN-α: OS (mature 2009 data)1

14

Total190/375200/375

0.0

0.2

0.4

0.6

0.8

1.0

0 6 12 18 24 30 36Time, months

OS

prob

abili

ty

Median OSSunitinib 26.4 monthsIFN-α 21.8 months

HR=0.82(95% CI=0.67–1.00)

Log-rank p=0.051

1. Motzer et al. J Clin Oncol 2009;27:3584–90.

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Pazopanib 800 mg QD continuous dosing

Dose reductions to 600 mg or 400 mg

Sunitinib 50 mg QD4 wks on/2 wks offDose reductions to 37.5 mg or 25 mg

Key Eligibility Criteria Advanced/metastatic RCC Clear-cell histology No previous systemic therapy Measurable disease (RECIST 1.0) KPS ≥ 70 Adequate organ function

Stratification factors KPS 70/80 vs 90/100 Previous nephrectomy Baseline LDH > 1.5 vs ≤ 1.5 x ULN

COMPARZ: Phase III Noninferiority Trial of Pazopanib vs Sunitinib in First-line mRCC

Randomized1:1

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Primary Endpoint: PFS (Independent Review)

N Median PFS, Mos (95% CI)

Pazopanib 557 8.4 (8.3-10.9)Sunitinib 553 9.5 (8.3-11.1)

HR: 1.047 (95% CI: 0.898-1.220)

Motzer RJ, et al. ESMO 2012. Abstract 2325.

Pts at Risk, n557553

361351

245249

136147

105111

6169

4648

1918

1310

13

PazopanibSunitinib

1.0

0.8

0.6

0.4

0.2

0Prop

ortio

n of

Pts

Pro

gres

sion

Fre

e

0 4 8 12 16 20 24 28 32 36 40Mos

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Interim Analysis of OSN Median OS, Mos

(95% CI)Pazopanib 557 28.4 (26.2-35.6)Sunitinib 553 29.3 (25.3-32.5)

HR: 0.908 (95% CI: 0.762-1.082;P = .275)

Motzer RJ, et al. ESMO 2012. Abstract 2325.

PazopanibSunitinib

1.0

0.8

0.6

0.4

0.2

0

Estim

ated

Sur

viva

l Fun

ctio

n

00 4 8 12 16 20 24 28 32 36 40Mos

44Pts at Risk, n

557553

521501

458431

384354

327313

274269

223225

142148

8269

33

2828

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Most Common Adverse Events (Treatment Emergent)

Adverse Event,* % Pazopanib (n = 554) Sunitinib (n = 548)All Grades Grade 3/4 All Grades Grade 3/4

Any event† > 99 59/15 > 99 57/17

Diarrhea 63 9/0 57 7/< 1

Fatigue 55 10/< 1 63 17/< 1

Hypertension 46 15/< 1 41 15/< 1

Nausea 45 2/0 46 2/0

Decreased appetite 37 1/0 37 3/0

ALT increased 31 10/2 18 2/< 1

Hair color changes 30 0/0 10 < 1/0

Hand–foot syndrome 29 6/0 50 11/< 1

Taste alteration 26 < 1/0 36 0/0

Thrombocytopenia 10 2/< 1 34 12/4

*Adverse event ≥ 30% in either arm.†2% of patients in pazopanib arm and 3% of patients in sunitinib arm had grade 5 adverse events.

Motzer RJ, et al. ESMO 2012. Abstract 2325.

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PISCES Patient Preference Study Design

2-wk washout

Wks

Treatment 2Treatment 1 Off study

0 4 12 2210

Primary endpoint – Patient preference

Secondary endpoints– Quality of life (EQ-5D)– Safety (FACIT-Fatigue)– Pharmacokinetics– Biomarkers

Sunitinib 50 mg 4/2,

10 wks

Pazopanib800 mg once daily,

10 wks

Sunitinib 50 mg 4/2,

10 wks

Pazopanib800 mg once daily,

10 wks

RandomizationPatient choiceof treatment to

progression

N = 160

ClinicalTrials.gov. NCT01064310.

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Primary Endpoint: Patient Preference Primary Analysis Population

70%

22%8%

Difference (pazopanib vs sunitinib) 49.3%

90% CI for difference 37.0% to 61.5%

P value < .001

Escudier BJ, et al. ASCO 2012. Abstract CRA4502.

90

80

30

20

10

0

Patie

nts

(%)

70

60

50

40

Pazopanib Preferred Sunitinib Preferred No Preference

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Side effects related to VEGFR inhibition1

Side effect Potential mode of action

HypertensionEffect on endothelial function (decreased nitric oxide synthesis)Inhibition of new arteriole and capillary formationVasoconstriction

Haemorrhage (bleeding events)

Decreased renewal capacity of endothelium in response to injury/traumaEndothelial cell apoptosis, which may lead to disruption of vascular structure, vascular rupture and haemorrhageTumour-associated bleeding as tumour regresses and detaches from blood vessels

Venous and arterial thromboembolic events

Endothelial cell apoptosis, resulting in exposure of subendothelial collagen and initiation of coagulation cascadeIncreasing PAI-1 expressionActivating endothelial cells, or increasing expression of pro-inflammatory genes in endothelial cells

Wound healing Reduces wound breaking strengthPrevents growth and maturation of new blood vessels vital to the healing process

Proteinuria Impedes glomerular repair or developmentPotentially related to hypertension

Gastrointestinal perforations

Underlying mechanism is unclear and likely to be multifactorialDelay in mucosal healingOther therapies such as corticosteroids may contribute

211. Porta and Szczylik. Cancer Treat Rev 2009;35:297–307.

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TKI-associated toxicities can have a negative effect on patients’ well-being

• Despite improved efficacy in the treatment of mRCC, TKIs are associated with several potentially distressing side effects, including:1,2

– Mucositis– Fatigue – Hand–foot syndrome– Diarrhoea

• Treatment-related side effects can have an adverse impact on:3,4

– Patients’ QoL and ability to carry out daily tasks– Efficacy of treatment– Healthcare resource use

• Recognition and prompt management of AEs are important to avoid unnecessary dose reductions that may negatively affect treatment efficacy1

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1. Hutson et al. Oncologist 2008;13:1084–96.2. Porta and Szczylik. Cancer Treat Rev 2009;35:297–307.3. Hudes et al. J Natl Compr Cancer Netw 2011;9:S1–29.4. Mickisch et al. Br J Cancer 2010;102:80–6.

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Even low-grade oral mucositis can have a negative effect on every day activities and QoL1,2

Grade 1 Sore mouth, no ulcers

Grade 2 Sore mouth with ulcers, but able to eat normally

Grade 3 Liquid diet only

Grade 4 Unable to eat or drink

231. Lalla et al. Dent Clin North Am 2008;52;61–77.2. Naidu et al. Neoplasia 2004;6:423–31.

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Fatigue can have a significant negative impact on everyday activities and QoL1,2

Grade 1 Fatigue relieved by rest

Grade 2 Fatigue not relieved by rest;limiting instrumental activities of daily living

Grade 3 Fatigue not relieved by rest; limiting self-care activities of daily living

241. Larkin et al. Oncologist 2010;15:1135–46.2. NCI CTCAE Version 4. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-

14_QuickReference_5x7.pdf (Last accessed January 2013).

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Even low-severity hand–foot skin reactions can negatively affect patients1

Grade 1 Minimal skin changes or dermatitis(e.g. erythema) without pain

Grade 2Skin changes (e.g. peeling, blisters, bleeding and oedema) or pain, limiting instrumental activities of daily living

Grade 3 Ulcerative dermatitis or skin changes with pain, interfering with function

251. NCI CTCAE Version 4. Available from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (Last accessed January 2013).

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Myelosuppression can affect QoL1 and may result in poor response to subsequent therapy2

• Myelosuppression associated with cancer therapy may lead to haematological abnormalities, including neutropenia or anaemia

• These abnormalities can lead to an increased risk of:1,2

– Fatigue– Diminished QoL – Reduced survival

• Anaemia appeared to be associatedwith a reduction in clinical benefitfrom second-line targeted therapy,according to a retrospectiveanalysis3

261. Larkin et al. Oncologist 2010;15:1135–46.2. Montoya. J Infus Nurs 2007;30:168–72.3. Elfiky et al. Urol Oncol 2011;29:756–63.

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ESMO 2016Copenhage - DenmarkOctober 7 - 11 2016

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ESMO-2016, Copenhagen, 7-11 October 2016

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ESMO-2016, Copenhagen, 7-11 October 2016

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AXIS Trial: Axitinib Superior to Sorafenibin Second-line mRCC Therapy

Rini BI, et al. Lancet. 2011;378:1931-1939.

1.00.90.80.70.60.50.40.30.20.1

00 2 4 6 8 10 12 14 16 18 20

Prob

abili

ty o

f PFS

AxitinibSorafenib

Median PFS, Mos (95% CI)6.7 (6.3-8.6)4.7 (4.6-5.6)

Stratified HR: 0.665(95% CI: 0.544-0.812; P < .0001)

Pts at Risk, nAxitinib

Sorafenib256224

361362

202157

145100

9651

6428

3812

206

103

11

00

Months

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RECORD-1: Everolimus (RAD001) in mRCC

• Primary endpoint: PFS(central review)• Secondary endpoints: safety, response rates, OS, QoL

Everolimus (RAD001) 10 mg QD(n = 272)

Placebo(n = 138)

RANDOMIZATION

Patients with mRCC following failure of VEGFR therapy,

clear-cell histology, previous therapy with sunitinib or sorafenib within 6 mos,

Karnofsky PS ≥ 70

Motzer RJ, et al. Lancet. 2008;372:449-456.

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Progression-Free Survival

Median PFS, MosEverolimus: 4.0

Placebo: 1.9

P < .0001

Motzer RJ, et al. Lancet. 2008;372:449-456.

100

80

60

40

20

00 2 4 6 8 10 12

Prob

abili

ty o

f PFS

(%)

EverolimusPlacebo

Pts at Risk, nEverolimus

Placebo13232

272138

474

81

20

00

00

Mos

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2014mRCC

L/I Risk

Sunitinib/Pazopanib

Axitinib

Everolimus

Long PFS

Short PFS

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Global ARCC: phase III study of temsirolimus alone, IFN-α alone or temsirolimus + IFN-α1

35

n=626

Primary endpointOS

Secondary endpointsPFSORRCBR

Eligibility criteria:Histologically confirmed, measurable (RECIST) advanced (stage IV or recurrent) RCCNo prior systemic therapyKPS≥60 Fasting serum cholesterol ≤350 mg/dl, triglycerides≤400 mg/dl≥3 poor-risk features

RANDOMISATION

Temsirolimus 25 mg IV weekly(n=209)

IFN-α escalating to 18 MIU SC3 × weekly (n=207)

Temsirolimus 15 mg IV weekly+ IFN-α 6 MIU SC 3 × weekly

(n=210)

1. Hudes et al. N Engl J Med 2007;356:2271–81.

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Global ARCC: phase III study of temsirolimus alone, IFN-α alone or temsirolimus + IFN-α1

36

Median OSTemsirolimus (n=209) 10.9 monthsIFN-α (n=210) 7.3 monthsTemsirolimus + IFN-α (n=207) 8.4 months

Tems vs IFN-αHR=0.73(95% CI=0.58–0.92)p=0.008

Tems + IFN-α vs IFN-αHR=0.96(95% CI=0.76–1.20)p=0.70

Number at riskTems 209 159 110 56 19 3 0Tems + IFN-α 210 135 93 50 17 7 2IFN-α 207 126 80 42 15 3 0

0 5 10 15 20 25 30 35Time, months

OS

prob

abili

ty

0.6

0

0.2

0.4

0.8

1.0

1. Hudes et al. N Engl J Med 2007;356:2271–81.

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Systemic Treatment For Clear-Cell RCC - 2014Setting Phase III Alternative

1st-Line Therapy

Good or intermediate

risk*

SunitinibPazopanib

Bevacizumab + IFN

HD IL-2

Poor risk* Temsirolimus Sunitinib

2nd-Line Therapy

Prior cytokine AxitinibSorafenib

Sunitinib or bevacizumab

Prior VEGFR inhibitor Everolimus Clinical Trials

Prior mTOR inhibitor Clinical Trials

*MSKCC risk status.

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PD-1/PD-L1 Checkpoint Blockade for Cancer Treatment

Ribas A. N Engl J Med. 2012;366:2517-2519.

Effector phase (peripheral tissue)

T-cell migration

T cell Cancercell

MHCTCR

PD-1

PD-L1

Cancer cellT cell

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Study design and endpoints

Disease assessments• Every 8 weeks from randomization through 12 months• Then every 12 weeks until progression or treatment discontinuationPrimary endpoint• Overall survival (OS)

Enrolled patients• Previously treated

advanced or metastatic clear-cell RCC

• 1 or 2 prior anti-angiogenic treatments R

ando

miz

e 1:

1

Nivolumab(N = 410)

3 mg/kg every 2 weeks intravenous

Everolimus (N = 411)

10 mg/day oral

• Treat until progression or intolerable toxicity

• Treatment beyond progression was permitted if drug was tolerated and clinical benefit was noted

Randomized, open-labeled phase III study to compare nivolumab with everolimus in patients with advanced RCC after prior systemic

therapy (NCT01668784)

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Overall survival

HR, hazard ratio; NE, not estimable.

Median OS, months (95% CI)

Nivolumab (N = 410) 25.0 (21.8–NE)

Everolimus (N = 411) 19.6 (17.6–23.1)

HR (98.5% CI), 0.73 (0.57–0.93)

P = 0.0018

0 3 6 129 15 18 21 24 27 30 330.0

0.3

0.1

0.2

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Ove

rall

Surv

ival

(Pro

babi

lity)

Nivolumab

Everolimus

The risk of death was reduced by 27% in patients in the nivolumab treatment group compared with those in the everolimus group

Study stopped after planned interim analysis (398 deaths) because assessment by an independent data monitoring committee concluded that the study met its primary endpoint, demonstrating superior OS for nivolumab

This means that patients are more likely to live when treated with nivolumab versus everolimus

Months

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Nivolumab Everolimus0

8

15

23

30

25

5

41

Objective response rate

Obj

ectiv

e R

espo

nse

Rat

e (%

)

P < 0.0001

Patients on nivolumab treatment had a significantly better objective response rate than those on everolimus treatment

This means that more patients responded to treatment with nivolumab than to treatment with everolimus

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▪ CheckMate 025 met its primary endpoint, demonstrating OS superiority with nivolumab versus everolimus

▪ This is the only phase III trial to demonstrate a survival advantage in previously-treated patients with mRCC versus standard therapy

▪ Nivolumab was associated with a greater number of objective responses than everolimus

▪ The survival improvement and favorable safety profile demonstrated in this phase III trial provides evidence for nivolumab as a potential new treatment option for previously treated patients with mRCC

▪ Based on the positive results of this trial, nivolumab was granted a breakthrough therapy designation from the FDA for advanced RCC, reinforcing the importance of these results in a patient population with large unmet medical need

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Key conclusions

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CheckMate 025: Phase III Study Design

▪ Primary endpoint: OS▪ Secondary endpoints: ORR, safety▪ Subgroup analyses: efficacy, safety from baseline to first progression and after

first progression

Pts with advanced RCC with clear-cell

component,KPS ≥ 70%, 1-2 previous

antiangiogenic agents,

progression ≤ 6 mos before enrollment

(N = 803)

Slide credit: clinicaloptions.comEscudier BJ, et al. ASCO 2016. Abstract 4509.

Nivolumab3 mg/kg IV Q2W

(n = 406)

Everolimus10 mg PO QD

(n = 397)

Progressed(n = 316)

Did not progress(n = 90)

Progressed(n = 320)

Did not progress(n = 77)

Treated beyond progression

(n = 153)Treated briefly

beyond progression (n = 18)

Not treated beyond progression

(n = 145)

Treated beyond progression

(n = 65)Treated briefly

beyond progression (n = 111)

Not treated beyond progression

(n = 144)

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CheckMate 025 Subgroup Analysis: OS

▪ Nivolumab appears to improve OS in pts treated beyond progression

Slide credit: clinicaloptions.comEscudier BJ, et al. ASCO 2016. Abstract 4509. Reproduced with permission.

153145

153131

146113

142101

13284

12369

9654

6529

3016

173

20

00

Pts at Risk, nTBPNTBP

TBP

Median OS, Mos (95% CI)TBPNTBP

HR: 0.41 (95% CI: 0.29-0.57)

0.4

1.0

0.8

0.6

0.2

00 3 6 9 12 15 18 21 24 27 30 33

Prob

abili

lty o

f OS

Mos

NTBP

28.1 (23.2-NE)15.0 (12.1-18.2)

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CheckMate 025 Subgroup Analysis: Change in Tumor Burden

▪ Postprogression nivolumab achieved reduced tumor burden in ~ 50% of evaluable pts (n = 142)

▪ In 14% (20/142), tumor burden reduced ≥ 30%; by contrast, 0/52 pts had tumor burden reduced ≥ 30% in the everolimus arm post progression

Slide credit: clinicaloptions.comEscudier BJ, et al. ASCO 2016. Abstract 4509. Reproduced with permission.

Asterisks represent responders before first progression. Square symbols represent % change truncated to 100%

50

25

0

-25

-50

-75

-100Bes

t Red

uctio

n Fr

om F

irst

Prog

ress

ion

in T

arge

t Les

ion

(%)

Pts

Best Reduction in Target Lesions With Nivolumab

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Long-term overall survival with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies.

McDermott DF, Proc ASCO 2016, Abstract 4507

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Long-term overall survival with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies.

McDermott DF, Proc ASCO 2016, Abstract 4507

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Long-term overall survival with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies.

McDermott DF, Proc ASCO 2016, Abstract 4507

Page 50: Estado actual de terapia sistémica en cáncer renal metastásico

Long-term overall survival with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies.

McDermott DF, Proc ASCO 2016, Abstract 4507

Page 51: Estado actual de terapia sistémica en cáncer renal metastásico

Long-term overall survival with nivolumab in previously treated patients with advanced renal cell carcinoma (aRCC) from phase I and II studies.

McDermott DF, Proc ASCO 2016, Abstract 4507

Page 52: Estado actual de terapia sistémica en cáncer renal metastásico
Page 53: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

Page 54: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

Page 55: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

Page 56: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

Page 57: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

Page 58: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

Page 59: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

Page 60: Estado actual de terapia sistémica en cáncer renal metastásico

Overall survival in METEOR, a randomized phase 3 trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

Choueiri TK, Proc ASCO 2016, Abstract 4506

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Terapia sistémica en mRCC - 2016Opciones y flujos

Pazopanib/Sunitinib

IL-2 altas dosis

Cabozantinib/Nivolumab

Axitinib

Everolimus

MSKCC riesgo alto Temsirolimus

MSKCC no riesgo alto

Sunitinib

Intolerancia/Progresión

Cada vez menos

Duplica supervivencia libre de progresión

Pobre pronóstico

Evidencia 1

Asignación de riesgo

Page 62: Estado actual de terapia sistémica en cáncer renal metastásico

Systemic Treatment For Clear-Cell RCC -2016

Setting Phase III Alternative

1st-Line Therapy

Good or intermediate

risk*

SunitinibPazopasnib

Bevacizumab + IFN

Cabozantinib (Phase II)

Poor risk* Temsirolimus Sunitinib

2nd-Line Therapy

Prior cytokine AxitinibSorafenib

Sunitinib or bevacizumab

Prior VEGFR inhibitor

CabozantinibNivolumab

EverolimusAxitinib

SorafenibPrior mTOR

inhibitor Cabozantinib/Nivolumab

Derived from Atkins. ASCO 2006 Plenary session; Figlin. Clin Adv Hematol Oncol. 2007;5:35; Escudier. Drugs. 2007;67:1257; Cho. Clin Cancer Res. 2007;13:761s; Atkins. Clin Cancer Res. 2005;11:3714.

*MSKCC risk status.

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@ONCONERD