algoritmo terapéutico en cáncer renal avanzado
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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
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
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…
Introducción
Introducción
PiezasdelPuzzleenCCRm
Sunitinib Sorafenib Interferon
Bevacizumab Pazopanib
Axitinib Everolimus Temsirolimus
PiezasdelPuzzleenCCRm
Sunitinib Sorafenib Interferon
Bevacizumab Pazopanib
Axitinib Everolimus Temsirolimus
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
¿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
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.
Para conocer la secuencia óptima, hay que saber los resultados de los fármacos en las diferentes
líneas de tratamiento
Primera Línea
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
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.
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
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
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)
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
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
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
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]
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.
Primera Línea
TKI
SEGUNDA LINEA
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
Secuencia de dos fármacos de la misma familia
Secuencia de dos fármacos con diferente actividad
Inhibidores de mTOR
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
RECORD-1: PFS and OS data
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)
Inhibidores de Tirosina quinasa
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
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
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
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
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
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
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)
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
Segunda Línea
TKI
El futuro…..
Nuevos fármacos
Objetivo Primario
Objetivos Secundarios
Tercera Línea
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.
Inhibidores de mTOR
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
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
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
Inhibidores de Tirosina quinasa
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)
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)
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
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
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
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
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
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
Tercera Línea
m-TOR
Conclusiones
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)
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?
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)
GRACIAS
Muchas gracias…
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