Ca. gastrico 2ª Lineas
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Transcript of Ca. gastrico 2ª Lineas
Reunión ClínicaCa. Gástrico
Segunda Línea
Dr. Daniel Agüero V
Modera: Dr. Marcelo Garrido
Diciembre 2017
Sexo: Masculino
Edad: 42 años
Procedencia: Ñuñoa
Actividad: Ing. Mecánico
Casado, 1 Hija
Caso Clínico:
Antecedentes Personales:
o Médicos: Hipotiroidismo
o Quirúgicos: Varicocele
o Médicamentos: Levotiroxina
o Tabaco: No Refiere
o OH: Ocasional
o Alergia: No Refiere
Antecedentes Familiares:
o Padre Colangiocarcinoma (>60a)
Caso Clínico:
Enero 2016 :
Dolor abdominal con baja de peso aprox 10Kg de 6m evolucion.
Hopitalizado por dolor no controlado
EDA: Mucosa infiltrada porNeoplasia
Biopsia: Adenocarcinomatubular poco diferenciado ulcerado IHQ : HER2 (+3)
TAC TAP 21.1.17: MxGanglionar, Peritoneal, SSRR
Caso Clínico:
Enero 2016 al Dg: Engrosamiento pared gástrica + LN
Retroperitoneales
LN Retroperitoneales + Mx SSRR
Diagnóstico
Cáncer Gástrico etapa IV cTxN1M1
Caso Clínico:
Abril 2016: RESPUESTA PARCIAL
02.16: CapeOx + Trastuzumab
Noviembre 2016: Hepática y SSRR
Primera Progresión:
Ramucirumab + FOLFIRI
REVISION:
2
11
30
17
5 Fluorouracil
Methotrexat
Mitomycin C
Doxorubicin
Cisplatin
Paclitaxel
Docetaxel
Irinotecan
19
21
24
31
0 10 20 30 40 50 60
Response Rate %
Activity Mono Chemotherapy Second Line
Advanced Gastric Cancer:
Caponigro et al, Front Biosci. 2005; 10: 3122-3126
5.2
3.8
5.2
3.6
Ramucirumab vs BSC[1]
(n = 355)
Docetaxel vs ASC[2]
(n = 131)
Chemo (docetaxel or irinotecan) vs BSC[3]
(n = 202)
Irinotecan vs BSC[4]
(n = 40)
5.3
1. Fuchs CS, et al. Lancet. 2014;383:31-39.
2. Ford H, et al. ASCO GI 2013. Abstract LBA4.
3. Kang JH, et al. J Clin Oncol. 2012;30:1513-1518.
4. Thuss-Patience PC, et al. Eur J Cancer. 2011;47:2306-2314.
3.8
4.0
2.4
0 1 2 3 4 5 6
Active treatment BSC/ASC
Median OS by Study Arm, Mos
Randomized Second-line Gastric Cancer
Studies (2009-2013): Median OS
Phase III REGARD Trial: BSC ± Ramucirumab
in Met Gastric or GEJ Cancer
Primary objective: OS
Secondary endpoints: PFS, 12-wk PFS, ORR, DoR, QoL, safety
Fuchs CS, et al. Lancet. 2014;383:31-39.
Pts with metastatic
gastric or GEJ
adenocarcinoma
progressing on first-line
platinum- and/or
fluoropyrimidine-
containing combination
therapy, ECOG PS 0-1
(N = 355)
Ramucirumab 8 mg/kg IV q2w +
BSC
(n = 238)
BSC + Placebo
(n = 117)
Treatment until
PD, unacceptable
toxicity, or death
Stratified by geographic region, weight loss (> vs < 10%
over 3 mos), location of primary tumor (gastric vs GEJ)
BSC ± Ramucirumab in Metastatic
Gastric or GEJ Cancer (REGARD): OS
Pts at Risk, n
Ramucirumab
Placebo
Pro
po
rtio
n R
em
ain
ing
Ali
ve
Mos
Ramucirumab Placebo
Pts/events 238/179 117/99
Median, mos 5.2 (4.4-5.7) 3.8 (2.8-4.7)
(95% CI)
6-mo OS, % 42 32
12-mo OS, % 18 11
HR: 0.776 (95% CI: 0.603-0.998; P = .0473)
1.0
0.8
0.6
0.4
0.2
0
0 2 4 6 10 14 208 12 171 3 5 7 11 15 169 13 18 19 26 2827
238
117
154
66
92
34
49
20
17
7
7
4
3
2
0
1
0
0
Ramucirumab
Placebo
Censored
Fuchs CS, et al. Lancet. 2014;383:31-39.
BSC ± Ramucirumab in Metastatic
Gastric or GEJ Cancer (REGARD): PFS,
ResponseP
rop
ort
ion
Wit
ho
ut
Pro
gre
ss
ion Ramucirumab
Placebo
Censored
Ramucirumab Placebo
Pts/events 238/199 117/108
Median, mos 2.1 (1.5-2.7) 1.3 (1.3-1.4)
(95% CI)
12-wk PFS, % 40 16
ORR, % 3 3
DCR, % 49 23
HR: 0.483 (95% CI: 0.376-0.620; P < .0001)
1.0
0.8
0.6
0.4
0.2
0
0 2 4 6 10 148 12 171 3 5 7 11 15 169 13
Mos
238
117
213
92
113
27
65
11
11
2
5
2
2
1
1
0
0
0
1
0
1
0
1
0
4
1
18
2
61
7
45
4
30
2
18
2
Pts at Risk, n
Ramucirumab
Placebo
Fuchs CS, et al. Lancet. 2014;383:31-39.
AE, % Ramucirumab (n = 236) Placebo (n = 115)
Any Grade Grade ≥ 3 Any Grade Grade ≥ 3
Hypertension*† 16 8 8 3
Bleeding/hemorrhage 13 3 11 3
Arteriothromboembolic 2 1 0 0
Venous thromboembolic 4 1 7 4
Proteinuria 3 < 1 < 3 < 0
GI perforation < 1 < 1 < 1 < 1
Fistula (GI and non-GI) < 1 < 1 < 1 < 1
Infusion-related reaction < 1 0 2 0
Cardiac failure < 1 0 0 0
*Includes increased blood pressure.†No grade 4 hypertension observed among ramucirumab-treated pts.
Fuchs CS, et al. Lancet. 2014;383:31-39.
BSC ± Ramucirumab in Metastatic
Gastric or GEJ Cancer (REGARD): AEs of
Interest
Wilke H, et al. Lancet Oncol. 2014;15:1224-1235.
RAINBOW: Second-line Paclitaxel ±Ramucirumab in Advanced Gastric Cancer
Randomized, double-blind phase III trial
Primary endpoint: OS
Secondary endpoints: PFS, ORR, TTP
Pts with metastatic or locally
adv unresectable gastric or
GEJ cancer and progression
on first-line chemo*
(N = 665)
Ramucirumab 8 mg/kg Days 1, 15 +
Paclitaxel 80 mg/m2 Days 1, 8, 15
(n = 330)
Placebo Days 1, 15 +
Paclitaxel 80 mg/m2 Days 1, 8, 15
(n = 335)
Stratified by geographic region,
measurable vs nonmeasurable disease,
TTP on first-line therapy (< 6 vs ≥ 6 mos)
Treat until
PD or
intolerable
toxicity
*Platinum agent plus fluoropyrimidine± anthracycline.
4-wk cycle
2nd-Line Ramucirumab in Advanced
Gastric Cancer (RAINBOW): OS
Δ mOS = 2.3 mos
Ram/Pac Placebo/Pac Ram
Pts/events, n 330/256 335/260 238/199
Median, mos 9.63 (8.48-10.81) 7.38 (6.31-8.38) 5.2 (4.4-5.7)
(95% CI)
6-mo OS, % 72 57 42
12-mo OS, % 40 30 18
HR: 0.807 (95% CI: 0.678-0.962; P = .0169)
1.0
0.8
0.6
0.4
0.2
0
0 4 8 12 16 20 24 28
Ram + PacPlacebo + PacCensored
Mos
Pro
ba
bil
ity o
f O
S
1. Wilke H, et al. Lancet Oncol. 2014;15:1224-1235.
2. Fuchs CS, et al. Lancet. 2014;383:31-39.
RAINBOW[1] REGARD[2]
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 2 6 10 14 18 22Mos
Ram + PacPlacebo + PacCensored
Pro
ba
bil
ity o
f P
FS
Ram/Pac Placebo/Pac Ram Pts/events, n 330/279 335/296 238/199Median, mos 4.40 (4.24-5.32) 2.86 (2.79-3.02) 2.1 (1.5-2.7)(95% CI)6-mo PFS, % 36 1712-mo PFS, % 22 10ORR, % 28 16 P = .0001 3DCR, % 80 64 P < .0001 49
HR: 0.635 (95% CI: 0.536-0.752; P < .0001)
Second-line Ramucirumab in Adv Gastric
Cancer (RAINBOW): PFS, Responses
1. Wilke H, et al. Lancet Oncol. 2014;15:1224-1235.
2. Fuchs CS, et al. Lancet. 2014;383:31-39.
RAINBOW[1] REGARD[2]
RAMIRIS: Ramucirumab + FOLFIRI vs
Ramucirumab +Paclitaxel in Metastatic Gastric CA
Lorenzen, Technische Universität München 2017
Randomized, double-blind, phase II trial
Primary endpoint: OS Rate after 6 months
Secondary endpoints: PFS, ORR, DCR, QoL
Pts with
metastatic
gastric/GEJ CA
cancer and
progression on
first-line chemo*
(N = 101)
Ramucirumab 8 mg/kg IV Days 1, 15
FOLFIRI FU 400mg/m2 Bolus, LV 400mg/m2
Irinotecan 180mg/m2 FU 2400 46 hrs infusion
continuous 1, 15
Ramucirumab 8 mg/kg IV Days 1, 15
Paclitaxel 80mg/m2 days 1, 8,15
28-day
cycles
*Platinum agent plus fluoropyrimidine (± anthracycline± Docetaxel±Trastuzumab)
ClinicalTrials.gov. NCT03081143.
Phase III Trials in Gastric Cancer:
EGFR-Targeted Agents
REAL3: ECX ± panitumumab (UK)[1]
– Negative: panitumumab had inferior outcomes
EXPAND: capecitabine/cisplatin ± cetuximab (EU)[2]
– Negative: cetuximab trended inferior
COG: BSC vs gefitinib (UK): negative[3]
Trials conducted with no biomarker selection of pts
– No biomarker identified in esophagogastric cancer
1. Waddell T, et al. Lancet Oncol. 2013;14:481-489.
2. Lordick F, et al. Lancet Oncol. 2013;14:490-499.
3. Dutton SJ, et al. Lancet Oncol. 2014;15:894-904.
Reunión ClínicaCa. Gástrico
Segunda Línea
Dr. Daniel Agüero V
Modera: Dr. Marcelo Garrido
Diciembre 2017