Estado actual de terapia sistémica en cáncer renal metastásico
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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
Mauricio Lema: Conflicto de interés
Honorarios por conferencias (2016): BMS, Servier, Roche, Novartis, MSD, Aztra-Zeneca, AMGEN, PfizerGrant de investigación:GSK/Novartis
@ONCONERD
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
CJ Creighton et al. Nature 000, 1-7 (2013) doi:10.1038/nature12222
Somatic alterations in ccRCC.
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
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
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.
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
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.
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.
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.
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.
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
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
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
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.
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.
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
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.
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
22
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.
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.
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).
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).
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.
ESMO 2016Copenhage - DenmarkOctober 7 - 11 2016
ESMO-2016, Copenhagen, 7-11 October 2016
ESMO-2016, Copenhagen, 7-11 October 2016
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
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.
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
2014mRCC
L/I Risk
Sunitinib/Pazopanib
Axitinib
Everolimus
Long PFS
Short PFS
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.
36
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.
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.
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
39
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)
40
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
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
42
▪ 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
43
Key conclusions
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
@ONCONERD
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