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Algoritmo terapéutico en Cáncer Renal Avanzado
Diego Soto de Prado y Otero
Hospital Clínico Universitario de Valladolid
Segovia, 7 de mayo de 2016
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ESQUEMA DE LA CHARLA
1. Introducción
2. Estudios en primera, segunda y tercera línea 3. Estudios de secuenciación y de series de pacientes
4. Conclusiones
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Introducción
● Al hacer un algoritmo terapéutico establecemos una secuencia de tratamientos.
● Hoy en día no existe una afirmación categórica sobre cual tiene que ser la secuencia optima de tratamiento en CCRm
● No obstante, aunque no existe una secuencia definida, nos podemos aproximar a cual puede ser la secuencia más óptima…
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Introducción
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Introducción
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PiezasdelPuzzleenCCRm
Sunitinib Sorafenib Interferon
Bevacizumab Pazopanib
Axitinib Everolimus Temsirolimus
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PiezasdelPuzzleenCCRm
Sunitinib Sorafenib Interferon
Bevacizumab Pazopanib
Axitinib Everolimus Temsirolimus
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ALGORITMO ÚTIL EN LA PRÁCTICA CLÍNICA A DÍA 7 DE MAYO DE 2016
QUIZÁ EN EL 2017 ESTE ALGORITMO CAMBIE CON LA INCORPORACIÓN DE NUEVOS
FÁRMACOS
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¿Cuando decidimos “nuestro” algoritmo de tratamiento?
1. Al inicio del tratamiento, teniendo un esquema prefijado (TKI-TKI-mTOR; TKI-mTOR-TKI)
- En base a la evidencia clínica - En base a la experiencia personal
2. Durante el tratamiento, en función de la respuesta a los mismos ó de la toxicidad de los fármacos
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Posibles algoritmos terapeúticos en Cáncer Renal metastásico
Poor prognosis
mRCC
mTOR inhibitor
Good/intermediate prognosis
VEGFR-TKI or MAb-VEGF-A
mTOR inhibitor
mTOR inhibitor
VEGFR-TKI
VEGFR-TKI
Eligible patients
First-line ~100%
Second-line ~40–60%1,2
Third-line <20%3–5
1. Levy et al. Eur J Cancer 2013; 2. Sonpavde et al. Eur Urol 2012; 3. Iacovelli et al. Eur J Cancer 2013; 4. Pal et al. ASCO GU 2013; 5. Heng et al. ASCO 2013
These slides are for internal use only. Should you wish to use externally, please ensure relevant permissions are obtained.
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Para conocer la secuencia óptima, hay que saber los resultados de los fármacos en las diferentes
líneas de tratamiento
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Primera Línea
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Relapseorstage4andmedicallyorsurgicallyunresectablePredominantclear-cellhistology
• Level 1 evidence* – Sunitinib – Bevacizumab + IFN-α – Pazopanib – Temsirolimus (for poor prognosis† patients)
• Level 2A evidence‡ – Clinical trial – High-dose IL-2 (for selected patients) – Sorafenib (for selected patients) – Best supportive care§
• Level 2B evidence** – Temsirolimus (for selected patients of other risk groups)
2016NCCNguidelinesforclear-cellmRCC:First-linetherapy
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Risk status Recommendation Level of evidence
Favorable or intermediate
Sunitinib Bevacizumab + IFN-α Pazopanib
I, A I, A I, A
Poor risk Temsirolimus II, A
First-linetreatmentguidelinesforclear-cellmRCC:ESMO2014
Escudier B, et al. Ann Oncol. 2014;25(Suppl 3):vii49–56.
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EnsayosClínicosenprimeralíneaStudy N ORR (%) Median PFS
(months) Final Median OS (months)
Phase III
Sunitinib vs. IFN-α 750 47 vs. 12 11 vs. 5 p<0.001
26.4 vs. 21.8 p=0.051
Bev + IFN-α vs. IFN-α 649 31 vs. 12 10.4 vs. 5.5 p<.0001
23.3 vs. 21.3 p =0.1291
Bev + IFN-α vs. IFN-α 732 25.5 vs. 13.1 8.4 vs. 4.9 p<0.0001
18.3 vs. 17.4 p =0.069
Pazopanib vs. placebo 233 32 vs. 3 11.1 vs. 2.8 p<0.0000001
22.9 vs. 23.55
p=0.525 Temsirolimus vs. IFN-α
626 8.6 vs. 4.8 5.5 vs. 3.1 p<0.001
10.9 vs. 7.3 p=0.0069
Pazopanib vs. sunitinib
1110 31 vs. 25 8.4 vs. 9.5 Non-inferior
28.4 vs. 29.3 Non-inferior
Phase II Sorafenib vs. IFN-α 189 5.2 vs. 8.7 5.7 vs. 5.6
p =0.504 NA
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Pivotal Phase III study of sunitinib first-line in mRCC
Eligibility Criteria • mRCC
• Clear-cell histology
• No prior systemic treatment
• Measurable disease by RECIST
• ECOG PS of 0–1
• Adequate organ function
Sunitinib 50 mg/day on schedule 4/2
(4 weeks on/ 2 weeks off)
IFN- α 3 MU s.c. t.i.w. 1st week 6 MU s.c. t.i.w. 2nd week 9 MU s.c. t.i.w. 3rd week
thereafter
(n=750)
(n=375)
(n=375)
R A N D O M I Z A T I O N
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Pivotal Phase III study of sunitinib first-line in mRCC
Motzer RJ, et al. N Engl J Med. 2007;356:115–124.
PFS by Independent Central Review
No. at risk Sunitinib: 375 240 156 54 10 1 IFN-α: 375 124 46 15 4 0
HR = 0.538 95% CI (0.439, 0.658) p<0.00001
0 5 10 15 20 25 30 Time, months
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
PFS
prob
abili
ty
Sunitinib Median: 11.0 months (95% CI: 10.7–13.4)
IFN-α"Median: 5.1 months (95% CI: 3.9–5.6)
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COMPARZ Study Design: Phase III, Open-label, Non-inferiority Trial
Motzer RJ, et al. N Engl J Med 2013;369(8):722–731
Pazopanib 800 mg QD Continuous daily dosing Enrolment criteria:
• Locally advanced or mRCC • Clear-cell histology • No prior systemic therapy • Measurable disease (RECIST 1.0) • KPS ≥70 • Adequate organ function Sunitinib 50 mg QD
Schedule 4/2
Randomised 1:1
N=1,110
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COMPARZ 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)
Pts at Risk, n 557 553
361 351
245 249
136 147
105 111
61 69
46 48
19 18
13 10
1 3
Pazopanib Sunitinib
1.0
0.8
0.6
0.4
0.2
0 Prop
ortio
n of
Pts
Pro
gres
sion
-Fre
e
0 4 8 12 16 20 24 28 32 36 40 Mos
Motzer RJ, et al. N Engl J Med 2013;369(8):722–731
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Sunitinib 50 mg/day**
RECORD-3 trial confirms first-line TKI is better than mTOR inhibitor
SCREEN
RANDOM I Z E *
Everolimus 10 mg/day
Sunitinib 50 mg/day**
Everolimus 10 mg/day
Study endpoints
Primary • PFS 1st-line Secondary • Combined PFS • ORR 1st-line • OS • Safety
1:1 Cross-over upon progression
N=471 First-line Second-line
*Stratified by MSKCC prognostic factors; **4 weeks on, 2 weeks off.
Motzer RJ et al. ASCO 2013; Abstract 4504.
Median follow-up 22.7 months
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RECORD-3: Primary endpoint: First-line PFS
Motzer RJ et al. ASCO 2013; Abstract 4504.
100 90 80 70 60 50 40 30 20 10 0
0 3 6 9 12 15 18 21 24 27 30 33 Time (months)
238 233
164 181
118 145
88 108
68 84
44 55
31 42
23 28
12 15
5 9
0 3
0 0
Number of patients still at risk Everolimus Sunitinib
Everolimus (events/N=182/238)
Sunitinib (events/N=158/233) Cum
ulat
ive
even
t-fre
e pr
obab
ility
(%) K-M Median PFS (mo)
Everolimus Sunitinib 7.85 10.71
HR = 1.43 Two-sided 95% CI [1.15, 1.77]
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RECORD-3: Overall survival 100
90
80
70
60
50
40
30
20
10
0
0 3 6 9 12 15 18 21 24 27 30 33 36
Cum
ulat
ive
even
t-fre
e pr
obab
ility
(%)
Time (months)
EVE→SUN (events/N=108/238)
SUN→EVE (events/N=96/233)
238
Number of patients still at risk
233
208
220
189
198
165
185
151
164
137
152
103
115
66
71
43
38
15
22
2
6
0
1
0
0
K-M Median OS (mo) EVE→SUN SUN→EVE
22.41 32.03
HR = 1.24 Two-sided 95% CI [0.94, 1.64]
EVE→SUN SUN→EVE
Motzer RJ et al. ASCO 2013; Abstract 4504.
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Primera Línea
TKI
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SEGUNDA LINEA
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After a first-line VEGF-targeted agent, what do you use?
Good/intermediate prognosis mRCC
VEGFR-TKI or MAb-VEGF-A
VEGFR-TKI? mTOR inhibitor?
Eligible patients
First-line ~100%
Second-line ~40–60%1,2
1. Levy et al. Eur J Cancer 2013; 2. Sonpavde et al. Eur Urol 2012
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Secuencia de dos fármacos de la misma familia
Secuencia de dos fármacos con diferente actividad
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Inhibidores de mTOR
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Everolimus phase III study (RECORD-1): design and enrolment criteria
Everolimus + BSC (n=272)
Placebo + BSC (n=138)
Upon disease progression
R A N D O M I S A T I O N
2:1
Escudier B, et al. ESMO 2008
§ Clear cell mRCC § Disease progression during
or within 6 months of stopping sunitinib and/or sorafenib
§ Prior cytokines and/or VEGFR inhibitors permitted
§ Stratification § Prior VEGFR-TKI § MSKCC prognostic
criteria
§ Primary endpoints: PFS (central review) § Secondary endpoints: Safety, ORR, OS, quality of life
N=410
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RECORD-1: PFS and OS data
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RECORD-1: ¿es representativo de una segunda línea?
● RECORD-1 80%: patients were treated with everolimus third-line or later
First- line
Second- line
Third- line
Fourth-line
mTOR fifth- line
n=82
n=104
n=141
n=89
First- line
Second- line
Third- line
mTOR fourth-
line
First- line
Second- line
mTOR third- line
First- line
mTOR second-
line
79%
21%
PFS: EVE: 4.9 months vs. PLC: 1.9 months (p<.001; HR=0.33)
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Inhibidores de Tirosina quinasa
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Treat until PD, unmanageable AE or withdrawal of consent Stratification: ● Prior regimen ● ECOG PS (0 vs 1)
Sorafenib 400 mg b.i.d.
Eligibility criteria: Histologically-confirmed mRCC with clear-cell component Failure of prior first-line regimen containing ≥1 of: • Sunitinib • Bevacizumab +IFN-α • Temsirolimus • Cytokine(s)
N=723
AXIS Phase III Study Design
Starting dose 5 mg BID with option for dose titration to 10 mg BID ● Primary endpoint: PFS ● Secondary endpoints: OS, ORR, duration of
response, safety, QoL (FKSI and EQ-5D)
RANDOM I Z A T I ON
Axitinib 5 mg b.i.d.
Rini BI, et al. Lancet 2011;378:1931–1939
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AXIS: Axitinib significantly prolonged PFS vs sorafenib
Updated data cut-off requested for SmPC June 03, 2011
Time (months) 0 2 4 6 8 10 12 22 24 26 28 14 16 18 20
PFS
(pro
babi
lity)
p<0.0001 (log-rank) Stratified HR=0.67 (95% CI: 0.56–0.81)
Axitinib Sorafenib
mPFS, months 95% CI 6.8 4.7
6.4–8.3 4.6–6.3
n 361 362
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0
Axitinib Summary of Product Characteristics, 2012
IRC Assessment
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AXIS: axitinib significantly improved PFS vs sorafenib in patients with prior sunitinib treatment
Axitinib SmPC, 2014
1.0
0.8
0.6
0.4
0.2
0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Time (months)
PFS
(pro
babi
lity)
p=0.0063 HR 0.74 (95% CI 0.58–0.94)
Axitinib Sorafenib
mPFS, months 95% CI 4.8 3.4
4.5–6.5 2.8–4.7
n* 194 195
PFS improvement from 3.4 to 4.8 months with axitinib vs sorafenib
*Prior sunitinib subgroup
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Patients with mRCC and PD on 1st-line
sunitinib (N=512)
Stratification factors: • Duration of sunitinib therapy (≤ or >6 mo) • MSKCC risk group • Histology (clear cell or non–clear cell) • Nephrectomy status
RANDOMIZE
Temsirolimus 25 mg IV weekly†
(n=259)
1:1
Sorafenib 400 mg oral BID†
(n=253)
Treat until PD, unacceptable
toxicity, or discontinuation for any other
reason
INTORSECT* Study Design
N=512 112 sites in 20 countries
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CI, confidence interval; HR, hazard ratio; IRC, Independent Review Committee; PFS, progression-free survival.
Temsirolimus Sorafenib
PFS
(pro
babi
lity)
252 72 22 11 6 0 259 96 28 9 5 0
Sorafenib Temsirolimus
Time (months) 0 5 10 15 20 25
Progression-Free Survival (IRC Assessment)
P=0.1933 (log-rank) Stratified HR: 0.87
(95% CI: 0.71, 1.07)
Median PFS, months 95% CI
4.28 3.91
4.01, 5.43 2.80, 4.21
Patients at risk, n
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
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Overall Survival O
vera
ll Su
rviv
al (p
roba
bilit
y)
253 158 74 34 13 0 259 132 54 22 8 0
Sorafenib Temsirolimus
0 10 20 30 40 50
Temsirolimus Sorafenib
Patients at risk, n Time (months)
P=0.014 (log-rank) Stratified HR: 1.31
(95% CI: 1.05, 1.63)
12.27 16.64
10.13, 14.80 13.55, 18.72
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
CI, confidence interval; HR, hazard ratio; OS, overall survival.
Median OS, months 95% CI
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Second-line median PFS is higher for VEGFR-TKI → VEGFR-TKI vs VEGFR-TKI → mTOR in comparative
retrospective studies
1. Heng et al. ASCO GU 2012; 2. Proskorovsky et al. Ann Oncol 2012; 3. Vickers et al. Urology 2010; 4. Weikert et al. J Clin Oncol 2011; 5. Derosa et al. Ann Oncol 2012; 6. Alimohamed et al. Clin Gen Cancer 2014
*Sunitinib → sorafenib; †Sorafenib → sunitinib
Heng et al. (N=818)
Proskorovsky et al. (N=318)
Vickers et al. (N=216)
Weikert et al. (N=108)
Derosa et al. (N=42)
Alimohamed et al. (N=818)
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Real-world experience: Second-line therapy at Institut Gustave Roussy (2005–2009)
● 62% of eligible mRCC patients (n=211) received second-line targeted therapy (most frequent first-line agent was sunitinib)
Median OS from start of second-line therapy
p=0.126
TKI (20.8 months)
mTOR (16.6 months)
1.00
0.80
0.60
0.40
0.20
0
Months
Pro
babi
lity
of O
S
0 6 12 18 24 30 36 42 48 54 60 66 72
Levy et al. Eur J Cancer 2013
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Segunda Línea
TKI
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El futuro…..
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Nuevos fármacos
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Objetivo Primario
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Objetivos Secundarios
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Tercera Línea
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Potential therapeutic algorithms for targeted agents in mRCC
Poor prognosis
mRCC
mTOR inhibitor
Good/intermediate prognosis
VEGFR-TKI or MAb-VEGF-A
mTOR inhibitor
mTOR inhibitor
VEGFR-TKI
VEGFR-TKI
Eligible patients
First-line ~100%
Second-line ~40–60%1,2
Third-line <20%3–5
1. Levy et al. Eur J Cancer 2013; 2. Sonpavde et al. Eur Urol 2012; 3. Iacovelli et al. Eur J Cancer 2013; 4. Pal et al. ASCO GU 2013; 5. Heng et al. ASCO 2013
These slides are for internal use only. Should you wish to use externally, please ensure relevant permissions are obtained.
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Inhibidores de mTOR
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RECORD-1: NOT representative of a pure second-line trial
The results of RECORD 1 indicate that a reasonable PFS may still be achieved with an mTOR inhibitor in third-line (or later)
1. Zustovich et al. Crit Rev Oncol Hematol 2012; 2. Motzer et al. Cancer 2010
79%
21%
1st- line
2nd- line
3rd- line
4th-line n=82
n=104
n=141
n=89
1st- line
2nd- line
3rd- line
1st- line
2nd- line
1st- line
mTOR 2nd- line
mTOR 3rd- line
mTOR 4th- line
mTOR 5th- line
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RECORD-1 data provide a strong rationale for using everolimus after two prior VEGFR-TKIs
1. Calvo et al. Eur J Cancer 2012
n Everolimus Placebo HR (95% CI)
1 prior VEGFR-TKI 308 5.4 1.9 0.32 (0.24–0.43) p<0.001
2 prior VEGFR-TKIs 108 4.0 1.8 0.32 (0.19–0.54) p<0.001
In RECORD-1, 108 patients (26%) had received two previous VEGFR-TKIs1,2
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Setting Risk group Standard Option
First line
Good/Intermediate risk Sunitinib [I,A]
Bevacizumab + IFN-α [I,A] Pazopanib [I,A]
High-dose IL2 [III,C] Sorafenib [II,B] Bevacizumab +
low-dose IFN-α [III,A]
Poor risk Temsirolimus [II,A] Sunitinib [II,B] Sorafenib [III,B]
Second line Post cytokines
Axitinib [I,A] Sorafenib [I,A]
Pazopanib [II,A] Sunitinib [III,A]
Post VEGFR-TKI Axitinib [I,B] Everolimus [II,A] Sorafenib [II,A]
Third line
Post two VEGFR-TKIs Everolimus [II,A]
Post VEGFR-TKI and mTOR inhibitor Sorafenib [I,B] Other VEGFR-TKI [IV,B]
Rechallenge [IV,B]
IFN-α, interferon-α; VEGFR, VEGF receptor Escudier et al. Ann Oncol 2014
2014 ESMO clinical practice guidelines
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Inhibidores de Tirosina quinasa
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GOLD: dovitinib versus sorafenib in VEGFR-TKI and everolimus-treated patients with mRCC
• Primary endpoint: PFS • Secondary endpoints: Safety, ORR, OS, QoL
Motzer et al. proc ESMO 2013 AbstrE17-7025
Dovitinib 500 mg PO 5D / 2D
(n=284)
Eligibility • mRCC (clear cell
component) • KPS > 70% • Failed two prior therapies
– VEGFR-TKI – mTORi
Stratification, by: • MSKCC prognostic criteria • Region
N=570 On disease progression
RANDOM I SA T I ON
Sorafenib 400 mg BID PO
(n=286)
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GOLD: progression-free survival
MotzerRJetal.LancetOncol2014;15:286–96.
0
20
40
60
80
100
Pro
porti
on o
f pat
ient
s pr
ogre
ssio
n-fre
e
0 3 6 9 12 15 18 21
Time from randomization (months)
Dovitinib Sorafenib
No. at risk 284 148 41 20 3 1 1 0 286 152 42 12 2 1 0 0
Dovitinib = 3.7 months (n=209) Sorafenib = 3.6 months (n=231)
HR (Dov/Sor) = 0.86 95% CI = 0.72–1.04 P=0.004 (one-sided)
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GOLD: overall survival
MotzerRJetal.LancetOncol2014;15:286–96.
0
20
40
60
80
100
OS
(% o
f pat
ient
s)
Time from randomization (months) 0 3 6 9 12 15 18 21
Dovitinib Sorafenib
No. at risk 284 246 165 102 51 23 9 0 286 242 160 95 52 22 7 0
Dovitinib = 11.1 months (n=130) Sorafenib = 11.0 months (n=135)
HR (Dov/Sor) = 0.96 95% CI = 0.75–1.22
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Setting Risk group Standard Option
First line
Good/Intermediate risk Sunitinib [I,A]
Bevacizumab + IFN-α [I,A] Pazopanib [I,A]
High-dose IL2 [III,C] Sorafenib [II,B] Bevacizumab +
low-dose IFN-α [III,A]
Poor risk Temsirolimus [II,A] Sunitinib [II,B] Sorafenib [III,B]
Second line Post cytokines
Axitinib [I,A] Sorafenib [I,A]
Pazopanib [II,A] Sunitinib [III,A]
Post VEGFR-TKI Axitinib [I,B] Everolimus [II,A] Sorafenib [II,A]
Third line
Post two VEGFR-TKIs Everolimus [II,A]
Post VEGFR-TKI and mTOR inhibitor Sorafenib [I,B] Other VEGFR-TKI [IV,B]
Rechallenge [IV,B]
IFN-α, interferon-α; VEGFR, VEGF receptor Escudier et al. Ann Oncol 2014
2014 ESMO clinical practice guidelines
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Patients who responded well on 1st line sunitinib, may benefit from re-exposure with sunitinib after a while
(RESUME Study)
First-line Median, 18.4 months (95% CI: 12.5–23.7) Rechallenge Median, 7.9 months (95% CI: 5.4–13.2)
95% confidence limits Censored
Time (months) No. of patients at risk
Prob
abili
ty o
f PFS
0 10 20 30 40 50 60
52 47 22 6 2 2 2 32 14 3 2 51 27 7 2 1 0 14 4 1 1
1.0
0.8
0.6
0.4
0.2
0.0
61 Oudard et al, Abstract No. 816PD, ESMO 2014
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Setting Risk group Standard Option
First line
Good/Intermediate risk Sunitinib [I,A]
Bevacizumab + IFN-α [I,A] Pazopanib [I,A]
High-dose IL2 [III,C] Sorafenib [II,B] Bevacizumab +
low-dose IFN-α [III,A]
Poor risk Temsirolimus [II,A] Sunitinib [II,B] Sorafenib [III,B]
Second line Post cytokines
Axitinib [I,A] Sorafenib [I,A]
Pazopanib [II,A] Sunitinib [III,A]
Post VEGFR-TKI Axitinib [I,B] Everolimus [II,A] Sorafenib [II,A]
Third line
Post two VEGFR-TKIs Everolimus [II,A]
Post VEGFR-TKI and mTOR inhibitor Sorafenib [I,B] Other VEGFR-TKI [IV,B]
Rechallenge [IV,B]
IFN-α, interferon-α; VEGFR, VEGF receptor Escudier et al. Ann Oncol 2014
2014 ESMO clinical practice guidelines
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Clinical outcomes in patients receiving three lines of targeted therapy for metastatic renal cell carcinoma:
Results from a large patient cohort
R. Iacovelli et al. European Journal of Cancer 2013;49(9):2134-2142
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La secuencia TKI–TKI–mTORi proporcionó mejores resultados que la secuencia TKI–mTORi–TKI
R. Iacovelli et al. European Journal of Cancer 2013;49(9):2134-2142
TKI-TKI–mTORi (n=152)
TKI–mTORi–TKI (n=95)
p value
Mediana PFS 36.5 meses (95% CI,30.5–42.6) 29.3 meses (95% CI, 23.6–34.9) p= 0.059
Mediana SG 50.7 meses (95% CI, 40.6–60.8) 37.8 meses (95% CI, 34.2– 41.5) p = 0.004
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Tercera Línea
m-TOR
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Conclusiones
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CONCLUSIONES
● En primera línea: Sunitinib y Pazopanib se perfilan como los tratamientos a valorar en la mayor proporción de pacientes
● En segunda línea: Axitinib a demostrado ser superior a Sorafenib. Everolimus eficaz en segunda línea y posteriores.Estudio INTORSEC
● Existen nuevos fármacos con eficacia en segunda línea:
ü La inmunoterapia (Nivolumab) es superior a m-TOR
ü Cabozantanib es eficaz pero cuidado con su toxicidad
● En tercera línea: Muy pocos pacientes. El tratamiento dependerá de los empleado en segunda línea (m-TOR)
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Mi algoritmo terapeútico en Cáncer Renal metastásico
Mal Pronóstico
mRCC
Temsirolimus
Pronóstico bueno/intermedio
Sunitinib / Pazopanib
Everolimus
Everolimus
Axitinib
Sorafenib
Primera línea
Segunda Linea
Tercera línea
Nivolumab Cabozantanib Axitinib
TKI / mTOR?
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Aunque no existe una recomendación clara sobre cual pude ser la
secuencia de tratamiento más beneficiosa, si podemos aproximarnos
a ella….
TKI – TKI (TKI-TKI-mTOR)
MEJORES RESULTADOS QUE
TKI-mTOR (TKI-mTOR-TKI)
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GRACIAS
Muchas gracias…