Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn...
Transcript of Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn...
![Page 1: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/1.jpg)
Tratamiento de combinación en el
melanoma irresecable o avanzado BRAF +
Dra. Ainara Soria Rivas
Servicio de Oncología Médica
![Page 2: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/2.jpg)
EVOLUCIÓN DEL TRATAMIENTO DEL MELANOMA
Combinaciones de
quimioterapia (CVD, Dartmouth)
1975 1980s 1998
DACARBAZINA IL 2
ALTAS DOSIS
2011
IPILIMUMAB
VEMURAFENIB TRAMETINIB COBIMETINIB
DABRAFENIB
NIVOLUMAB PEMBROLIZUMAB
NIVOLUMAB- IPILIMUMAB
ENCORAFENIB BINIMETINIB
2017
![Page 3: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/3.jpg)
![Page 4: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/4.jpg)
HALLMARKS OF CANCER
Hanahan D, Weingerg RA. Cell 2000 Jan 7;100(1):57-70. Hanahan D, Weinberg RA. Cell 2011. Vol144 (5): 646-674.
![Page 5: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/5.jpg)
VIA DE LAS MAP KINASAS
Dermatol Ther 2015 Sep 5
![Page 6: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/6.jpg)
Salama A K , and Flaherty K T Clin Cancer Res 2013;19:4326-4334
![Page 7: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/7.jpg)
N Engl J Med 2014
N Engl J Med 2015
![Page 8: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/8.jpg)
COMBI-D: Supervivencia libre de progresión
Flaherty K. ASCO 2016
![Page 9: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/9.jpg)
Robert C. ESMO 2016.
![Page 10: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/10.jpg)
COMBI-D: Supervivencia global
Flaherty K. ASCO 2016 58% de los pacientes vivos, se encuentran en tratamiento con D +T
![Page 11: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/11.jpg)
Robert C. ESMO 2016.
![Page 12: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/12.jpg)
![Page 13: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/13.jpg)
COMBI-v: Best Response
14
Best Confirmed Response
Dabrafenib + Trametinib (n = 352)
Vemurafenib (n = 352)a
Overall response rate, n (%) [95% CI]
236 (67) [62-72]
187 (53) [48-58]
Complete response (CR), n (%) 68 (19) 41 (12)
Partial response (PR), n (%) 168 (48) 146 (41)
Stable disease (SD), n (%) 83 (24) 109 (31)
Progressive disease, n (%) 22 (6) 37 (11)
Not evaluable, n (%) 11 (3) 18 (5)
Robert C. ESMO 2016.
![Page 14: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/14.jpg)
COMBI-v: Duration of Response
15
● 36 of 68 patients (53%) with a CR on dabrafenib + trametinib are still in CR ● 21 of 41 patients (51%) with a CR on vemurafenib are still in CR
Pat
ien
ts
Survival, months
0 10 20 30 40
Dabrafenib + Trametinib
0 10 20 30 40
Survival, months
Pat
ien
ts
Vemurafenib
Median DOR (95% CI), months Dabrafenib + Trametinib Vemurafenib
All responders (CR + PR) 13.8 (11.3-17.7) 7.9 (7.4-9.3)
Complete responders 39.6 (26.5-NR) 29.9 (16.7-NR)
Partial responders 10.8 (9.2-12.0) 7.3 (5.8-7.5)
Complete response
Partial response
Complete response
Partial response
Robert C. ESMO 2016.
![Page 15: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/15.jpg)
Robert C. ESMO 2016
![Page 16: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/16.jpg)
Flaherty K. ASCO 2016
![Page 17: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/17.jpg)
COMBI-v: Post-Progression Systemic Therapy
18
Post-Progression Systemic Therapy Dabrafenib + Trametinib
(n = 187) Vemurafenib
(n = 248)
Subsequent anticancer therapy, n (%)
Immunotherapy 108 (58) 123 (50)
Ipilimumab 88 (47) 100 (40)
Nivolumab 3 (2) 3 (1)
Pembrolizumab 14 (7) 13 (5)
Radiotherapy 102 (55) 120 (48)
Small-molecule targeted therapy 59 (32) 115 (46)a
Chemotherapy 43 (23) 71 (29)
Biologic therapy 14 (7) 12 (5)
Hormonal therapy 0 2 (< 1)
Median time from study treatment discontinuation to start of subsequent systemic therapy
12 days 11 days
● A total of 187 patients (53%) in the dabrafenib + trametinib arm and 248 patients (70%) in the vemurafenib arm received post-study anticancer therapy
a Includes patients who crossed over from vemurafenib to dabrafenib + trametinib. Robert C. ESMO 2016.
![Page 18: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/18.jpg)
IMPACTO DE LOS FACTORES PRONÓSTICOS…
![Page 19: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/19.jpg)
COMBI-v: Complete Responders—Baseline Characteristics
20
Dabrafenib + Trametinib (n = 68) Vemurafenib (n = 41)
Median age (range), years 59 (26-80) 50 (23-79)
Male sex, n (%) 35 (51) 15 (37)
ECOG PS, n (%) 0/1
62 (91)/5 (7)a
32 (78)/9 (22)
BRAF V600 mutation status, n (%) V600E mutation–positive V600K mutation–positive
64 (94)
4 (6)
40 (98)
1 (2)
Metastasis stage at screening, n (%)b M0 M1a M1b M1c
6 (9)
18 (27) 17 (25) 26 (39)
2 (5)
15 (37) 5 (12)
18 (44)
Baseline LDH, n (%) ≤ ULN/> ULN
64 (94)/4 (6)
36 (88)/5 (12)
Visceral disease at baseline, n (%) Yes/No
44 (66)/23 (34)
24 (59)/17 (41)
Number of organ sites with metastasis, n (%) < 3/≥ 3
57 (84)/11 (16)
37 (90)/4 (10)
a One patient had missing ECOG PS at baseline; b One patient in the Vem arm had a metastasis stage of MX at screening.
![Page 20: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/20.jpg)
![Page 21: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/21.jpg)
![Page 22: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/22.jpg)
COMBI-v: Elevated LDH (> ULN)
23
OS PFS
OS
Pro
bab
ility
Dabrafenib + trametinib (n = 119) Median OS, 10.8 (95% CI, 8.9-14.4)
HR, 0.79 (95% CI, 0.59-1.07)
3-y OS, 20%
3-y OS, 14%
2-y OS, 27%
2-y OS, 25%
PFS
Pro
bab
ility
Months From Randomization
Dabrafenib + trametinib (n = 119) Median PFS, 5.5 (95% CI, 5.3-7.3)
Vemurafenib (n = 114) Median PFS, 4.0 (95% CI, 3.7-5.4)
3-y PFS, 6%
3-y PFS, 3%
2-y PFS, 13%
2-y PFS, 4%
HR, 0.70 (95% CI, 0.53-0.93)
Months From Randomization
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36 42
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36
119 114
90 77
52 37
38 31
27 23
20 16
15 10
3 3
119 114
49 32
26 12
15 7
13 3
12 3
4 2
Patients at risk, n D + T Vem
Patients at risk, n D + T Vem
Vemurafenib (n = 114) Median OS, 8.7 (95% CI, 7.3-10.7)
Robert C. ESMO 2016.
![Page 23: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/23.jpg)
COMBI-v: Normal LDH (≤ ULN)
24
Patients at risk, n D + T Vem
Patients at risk, n D + T Vem
Months From Randomization
Dabrafenib + trametinib (n = 233) Median OS, NR (95% CI, 35.1-NR)
3-y OS, 56%
3-y OS, 39%
2-y OS, 66%
2-y OS, 46%
Months From Randomization
Dabrafenib + trametinib (n = 233) Median PFS, 17.5 (95% CI, 14.9-21.2)
Vemurafenib (n = 238) Median PFS, 9.2 (95% CI, 7.6-10.9)
HR, 0.56 (95% CI, 0.44-0.70)
3-y PFS, 33%
3-y PFS, 13%
2-y PFS, 39%
2-y PFS, 21%
OS
Pro
bab
ility
PFS
Pro
bab
ility
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36 42
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36 42
233 238
221 212
193 166
163 123
144 96
130 87
112 71
30 19
233 238
187 130
136 70
105 48
80 24
68 13
59 9
25 2
Vemurafenib (n = 238) Median OS, 21.6 (95% CI, 18.2-26.4)
HR, 0.61 (95% CI, 0.47-0.79)
NR, not reached.
OS PFS
Robert C. ESMO 2016.
![Page 24: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/24.jpg)
![Page 25: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/25.jpg)
COMBI-v: Normal LDH and < 3 Organ Sites With Metastasis
26
Patients at risk, n D + T Vem
OS
Pro
bab
ility
Months From Randomization
Vemurafenib (n = 161) Median OS, 26.4 (95% CI, 21.5-46.8)
HR, 0.47 (95% CI, 0.33-0.67)
3-y OS, 70%
3-y OS, 46% 2-y OS, 52%
2-y OS, 79%
Dabrafenib + trametinib (n = 141) Median OS, NR (95% CI, NR-NR)
141 161
135 146
125 125
115 91
104 75
96 68
83 58
21 16
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36 42
Patients at risk, n D + T Vem
Months From Randomization
3-y PFS, 39%
3-y PFS, 16%
2-y PFS, 46%
2-y PFS, 27% Vemurafenib (n = 161) Median PFS, 10.7 (95% CI, 9.0-11.1)
HR, 0.52 (95% CI, 0.39-0.70)
PFS
Pro
bab
ility
Dabrafenib + trametinib (n = 141) Median PFS, 23.0 (95% CI, 18.1-29.7)
141 161
123 93
98 50
76 40
59 22
49 12
43 8
19 2
1.00
0.75
0.50
0.25
0.00
0 6 12 18 24 30 36 42
OS PFS
Robert C. ESMO 2016.
![Page 26: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/26.jpg)
POOLED ANALYSIS DABRAFENIB-TRAMETINIB
27
• Phase 1/2: dabrafenib + trametinib1
• COMBI-d: dabrafenib + trametinib vs dabrafenib2
• COMBI-v: dabrafenib + trametinib vs vemurafenib3
Pooled
Analysis
Overall Survival (OS) Median (95% CI), mo
Phase 1/2 D + T 25.0 (17.5–36.5)
COMBI-d D + T 25.1 (19.2–NR)
COMBI-d D + P 18.7 (15.2–23.7)
COMBI-v D + T 25.6 (22.6–NR)
COMBI-v V 18.0 (15.6–20.7)
Months
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
OS
Pro
babili
ty
Long G, et al. Lancet Oncol Dec 2016
![Page 27: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/27.jpg)
Methods: Patients
28
Study Randomize
d, na
PFS
Events, n
OS Events,
n
COMBI-v 352 215 155
COMBI-d 211 139 99
Phase 1/2 54 42 36
TOTAL 617 396 290
• Median duration of follow-up was 20.0 months
• 221 (36%) patients remained progression-free and alive
at analysis
BID, twice daily; PFS, progression-free survival; QD, once daily.
a Intention-to-treat population.
• Treatment-naive patients randomized to dabrafenib 150mg
BID + trametinib 2mg QD:
PRESENTED BY GV LONG AT SMR 2015
![Page 28: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/28.jpg)
Five Baseline Factors Influenced OS
29
ECOG = 0 ECOG ≥ 1
N = 93
1Y = 71%
2Y = 43%
3Y = NE
N = 56
1Y = 42%
2Y = 19%
3Y = 16%
LDH Normal LDH ≥ ULN N = 617
Disease Sites ≥ 3 Disease Sites < 3
N = 161
1Y = 76%
2Y = 55%
3Y = 38%
N = 237
1Y = 90%
2Y = 75%
3Y = 70%
LDH >1-≤ 2 × ULN LDH ≥ 2 × ULN
N = 70
1Y = 40%
2Y = 7%
3Y = 7%
N = 149
1Y = 60%
2Y = 33%
3Y = 9%
N = 219
1Y = 54%
2Y = 25%
3Y = 7%
N = 398
1Y = 85%
2Y = 67%
3Y = 57%
a Regression tree analysis.
NE, not estimable. PRESENTED BY GV LONG AT SMR 2015
![Page 29: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/29.jpg)
OS by LDH, Number of Disease Sites, and ECOG
30
Normal LDH, Disease Sites < 3 Normal LDH, Disease Sites ≥ 3
LDH > 1 x ULN, ECOG = 0 LDH > 1 x ULN, ECOG ≥ 1
LDH > 2 x ULN
a Factors identified by the regression tree analysis.
237 206 103 14
161 119 58 5
93 61 15 0
56 23 9 1
70 22 1 0
No. at risk
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36
OS
Pro
ba
bili
ty
Months
Normal LDH, Disease Sites < 3
Normal LDH, Disease Sites ≥ 3
LDH >1-≤ 2 x ULN, ECOG = 0
LDH >1-≤ 2 x ULN, ECOG ≥ 1
LDH > 2 x ULN
PRESENTED BY GV LONG AT SMR 2015
![Page 30: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/30.jpg)
Four Baseline Factors Influenced PFS
31
LDH Normal LDH ≥ ULN
N = 617
LDH >1-≤ 2 × ULN
LDH ≥ 2 × ULN
N = 149
1Y = 32%
2Y = 18%
3Y = 18%
N = 70
1Y = 8%
2Y = 2%
3Y = 2%
Disease Sites < 3 Disease Sites ≥ 3
N = 161
1Y = 50%
2Y = 29%
3Y = 17%
N = 237
1Y = 68%
2Y = 46%
3Y = 42%
N = 219
1Y = 24%
2Y = 13%
3Y = 13%
N = 398
1Y = 61%
2Y = 40%
3Y = 33%
a Regression tree analysis. PRESENTED BY GV LONG AT SMR 2015
![Page 31: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/31.jpg)
PFS by LDH and Number of Disease Sites
32
No. at risk
Normal LDH, Disease Sites < 3 Normal LDH, Disease Sites ≥ 3
LDH > 1 x ULN
LDH > 2 x ULN
a Factors identified by the regression tree analysis.
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36
237 149 53 8
161 69 23 2
149 40 9 0
70 4 0 0
PF
S P
rob
ab
ility
Months
Normal LDH, Disease Sites < 3
Normal LDH, Disease Sites ≥ 3
LDH >1-≤ 2 x ULN
LDH > 2 x ULN
PRESENTED BY GV LONG AT SMR 2015
![Page 32: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/32.jpg)
ENSAYOS POR VENIR…
![Page 33: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/33.jpg)
Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by
Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma
National Cancer Institute (NCI)
NCT02224781
IPILIMUMAB + NIVOLUMAB
DABRAFENIB + TRAMETINIB
IPILIMUMAB + NIVOLUMAB
DABRAFENIB + TRAMETINIB
Progresión o toxicidad
Progresión o toxicidad
Primary Outcome: OS rate, defined as the proportion of patients alive after 2 years of follow-up time. Secondary Outcome: PFS, evaluated based on RECIST version 1.1 Response rate according to RECIST version 1.1 Toxicity rate
Arm A
Arm B
![Page 34: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/34.jpg)
![Page 35: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/35.jpg)
![Page 36: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/36.jpg)
![Page 37: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/37.jpg)
![Page 38: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/38.jpg)
![Page 39: Tratamiento de combinación en el melanoma irresecable o ... › wp-content › ... · evoluciÓn del tratamiento del melanoma combinaciones de quimioterapia (cvd, dartmouth) 1975](https://reader030.fdocuments.es/reader030/viewer/2022040616/5f18d700878c4b55b827ba7b/html5/thumbnails/39.jpg)
CONCLUSIONES
• Dabrafenib y Trametinib han demostrado:
– Aumentar la SLP (12,1 meses).
– Aumentar la supervivencia global (26,1 meses).
• Alta tasa de respuestas: ORR 69% (16% RC) y 24% EE.
• Factores de buen pronóstico: LDH normal y menos de 3 localizaciones preciden un beneficio más prolongado del tratamiento y mayor probabilidad de respuesta completa.