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