Avances en el Tratamiento del Cáncer Gástrico y Esofágico 11.2.pdf · QT/RT de inducción en CE:...

Avances en el Tratamiento del Cáncer Gástrico y Esofágico

Fernando Rivera HerreroHospital Universitario Marqués de Valdecilla. Santander

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TIMER

• Introducción• Tratamiento de la Enfermedad Resecable

– Ca. Esofago– Adenoca Gástrico– Adenoca de la UEG– Nuevas dianas

• Tratamiento de la Enfermedad Avanzada– Ca. Epidermoide de esófago– Adenoca del esofago distal, la UEG y gástrico

• Quimioterapia• Nuevas dianas

Avances en el tratamiento del Cáncer Gástrico y Esofágico

Cáncer Esófago-Gástrico Grupo heterogéneo de enfermedades

Cáncer de esófago

- Ca. Epidermoide- Adenocarcinoma

Adenocarcinoma de la UEG

Adenoca. Gástrico

Gastric Cancer: Comprehensive Molecular Characterization

Esophageal Cancer Gastric CancerPts 5y OS* Pts 5y OS*

Early disease 10% 70% 10% 70%(T1-2 N0 M0)

Locally advanced 50% 30% 40% 30%resectable (T3-4, N+, M0) Locally advanced 25%

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Treatment options in Resectable -Esophageal Cancer

- EGJ Adenocarcinoma- Gastric Adenocarcinoma

- Definitive chemoradiotherapy- Preoperative Chemotherapy- Preoperative Chemo-RadiotherapyEsophageal

Cancer

Gastric Cancer

- Perioperative Chemotherapy- Postoperative Chemo-Radiotherapy- Postoperative Chemotherapy ??

- Preoperative Chemo-Radiotherapy- Perioperative Chemotherapy




Cancer

Definitive Chemo-Radiotherapy

F III RTOG 85-01: QT/RT vs RT(Herskowic, N Engl J Med, 1992)

123 pts(87% Squamous)

RT (64 Gy)

LR control (5y) 34% 53%P

QT/RT definitiva en C. Esófago

267 PTSCa esófago (Epid/Aden)Est I-IVA

CF/RT4 ciclos, 2 concomitantes

con 50Gy de RT

FOLFOX /RT6 ciclos, 3 concomitantes

con 50Gy de RT

F. III PRODIGE 5/ACCORD 17 1

Objetivo 1º: SLP (mediana) 9,7 m HR 0,93; p 0,64 9,4 mFOLFOX/RT menos tóxico

102 PTSCa esófago (Epid/Aden)Est I-IVA

CF/RTCarbo-Pacli /RT

E. Retrospectivo holandés (no randomizado) 2

Sv (mediana) 13,8 m HR 0,97; p 0,87 16,1 mSLP (mediana) 9,7 m HR 0,93; p 0,76 11,1 m

Carbo-Pacli/RT menos tóxico

1.- Conroy T et al. Lancet Oncology 2014; 2.- Honing J et al. Ann Oncol 2014

QT/RT de inducción en CE: CisFu vs CarboPacliE. Retrospectivo; 101 pts, 33% epidermoides

Global Tiende a más Sv CF

Resecados Similar Sv (CP menos tóxico)

Sim HW et al. ASCO 2017

No Resecados Mejor Sv con CF




Cancer

QT vs QT/RT Preoperatoria en Ca Esófago

Estudios / pts10 1209

SupervivenciaHR 0,81(0,7-0,93) p 0,002

Dif absoluta Sv 2a13 %

Meta-análisis Gebski et al, Lancet Oncology 07

Estudios / pts8 1724

SupervivenciaHR 0,9(0,81-1) p 0,05

Dif absoluta Sv 2a7 %

QT/RT preCx

QT preCx

Is it possible to avoid Surgeryafter CT/RT?

- In all patients?

QT/RT Surgery vs QT/RT

Phase III Stahl (Stahl, J Clin Oncol 2005)(only Squamous) 172 pts

Loco-Regional Control Survival

Is it possible to avoid Surgeryafter CT/RT?

- Only in initially responding patients?

Phase III FFCD 9102 (Bedenne et al, J Clin Oncol, 2007)

Phase III: FFCD 9102(Bedenne, J Clin Oncol, 2007)

Resectable Stage II-IV (M0)Squamous 90% 455 pts received CFx2 / 46Gy

PR: 259 pts

Sv (2y) 34% p NS 40%LRC(2y) 66,4 p NS 57%Treat.Mortality 9% 1%Q of L better

Surgery CT/RTCFx1 / 20Gy

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Treatment optionsin Resectable Gastric Cancer

Gastric Cancer

- Postoperative Chemotherapy -Postoperative Chemo-Radiotherapy - Perioperative Chemotherapy

GASTRIC “GLOBAL ADVANCED/ADJUVANT STOMACH TUMOR RESEARCH THROUGH INTERNATIONAL COLLABORATION”

JAMA. 201 0 MAY 5;303(1 7): 1 729- 37

Meta-Analysis 17 phase III trials 3 838 ptsIndividual data

HR: 0,82 (0,76-0,90)

5y OS: 55% vs 49%

Sakuramoto S et al, NEJM-07

1059 PTSR0 Resected Gastric adenocarc.St II-IV, D2+ nodal dissection No Postop

treatmentPostoperative S-1(S1 80mg/m2/d,

d 1-28 each 42d, 1 year)

Postoperative Chemotherapy: S-1Phase III ACTS-GC (Japan)

Primary endpoint: Sv

S1 No CT HR p Sv (3y) 80% vs 70% 0.68 0.003

Postoperative Chemotherapy

1035 PTSR0 resected Gastric cancer, D2St II-IIIB SurgerySurgery XELOX

Primary endpoint: SLP

Phase III CLASSIC (Asia)

HR p . SLP (5y) 73% 0.58

Treatment optionsin Resectable Gastric Cancer

Gastric Cancer

- Postoperative Chemotherapy -Postoperative Chemo-Radiotherapy - Perioperative Chemotherapy

Postoperative Chemo-RadiotherapySWOG 9008/INT 0116

Macdonald et al, N Engl J Med 2001

566 PTSR0, St.IB-IV (M0)

Gastric 80% E-G Junction 20% No Postop

treatmentCT/RTFU-Lv x5 / (45 Gy)

Sv (3 y) 50% p=0.005 41%Loc.Relap(3y) 19% p=0.005 29% Dist.Relap(3y) 33% 18%

Survival

INT 0116Survival according to Histology

Intestinal (61% of pts) Diffuse (39% of pts)

Macdonald et al, ASCO 2004

Smalley et al , J Clin Oncol 2012

Postoperative Chemo-Radiotherapy

546 PTS R0 resected Gastric C.

Surgery ECFx2F/RTECFx2

Surgery FLx2F/RTFLx2

Primary endpoint: OS

P. III CALGB 80101(US-Intergroup)

- Survival (median/3y) 37m /50% HR 1,03 p 0,8 38m/52%- DFS (median/3y) 30m /46% HR 1,03 p 0,8 28m/47%- G 4 Tox 40% p

Postoperative Chemo-Radiotherapy vs Postop Chemotherapy

- DFS (7y) 67% HR 0,74 p 0,09 73%- LR relapse 13% p 0,03 7%- OS (7y) 73% HR 1,13 p 0,52 75%

458 PTS R0 resected Gastric cancer, D2St II-IV

SurgeryXP/RTSurgery XP

P. III ARTIST (Korea)

1º endpoint: DFS

Park SH et al, J Clin Onc 2015

OS

P. III ARTIST (Korea)

Park SH et al, J Clin Onc 2015

PIII ARTIST-2Adj CT vs CT/RT in pN+ resected gastric cancer

Role of RT in diffuse?

POSTOPERATIVE CHEMO-RADIOTHERAPY VS POSTOP CHEMOTHERAPY



Gastric Cancer

- Postoperative Chemotherapy ??-Postoperative Chemo-Radiotherapy - Perioperative Chemotherapy

Perioperative Chemotherapy MAGIC-1

Cunningham et al, N Engl J Med 2006

503 PTSResectable St. II-IV (M0)Gastric 74% E-G Junction 26%

SurgeryPerioperative CTECFx3Surg.ECFx3

(44% of pts)

Sv (3y) 43% p

Boige V et al, ASCO-07 # 4510

224 PTSResectable adenocarcinoma -Gastric (no EGJ) 25 % -EGJ 64 %-distal esophagous 11 %

PS 0 / 1 (75% / 25%)

SurgeryPerioperative CTCFx2-3Surgery(CF x4 postSx if OR or SD with pN+: 50% pts)

CFSur Sur HR p Sv (5y) 38% vs 24% 0,66 0,01DFS (5y) 34% vs 21% 0,65 0,003

Perioperative ChemotherapyPhase III FNLCC-ACCORD07-FFCD 9703

Primary endpoint: Sv

Perioperative ChemotherapyP III FLOT4

Al-Batran SE, ASCO 2017

716 PTSResectable St. II-IV (M0)Gastric 44% E-G Junction 56% Perioperative ECX/F

ECX/Fx3Surg.ECX/Fx3

(completed 44% of pts)

Perioperative FLOTFLOTx4Surg.FLOTx4

(completed 51% of pts)

DFS (5 y) 31% HR 0.75 p 0.004 41%OS (5 y): 36% HR 0.77 p 0.012 45%No relevant difference in toxicity

SurvivalDFS

Should RT be added to perioperative CT?

788 PTSResectable Gastric Cancer St. II-IV (M0)

Primary end point: Survival

Perioperative CTECX x3Surg. ECX x3

Preop CT + Postop CT/RTECX x3Surg. RT/Xeloda

F. III CRITICS (Dutch)

OS (5 y) 40.8 m p 0,99 40.9 mPFS (5 y) 38.5% p 0,99 39.5 %

Verheij et al, ASCO 2016. Abstr 4000

1º endpointOS

PFS

Should RT be added to perioperative CT?

- The addition of RT to Perioperat CT remains “investigational”- Waiting for Subgroup analysis of CRITICS

752 PTSResectable Gastric Cancer

T3-4 and/or N+ (M0)Primary end point: Survival

Perioperative CTECF x3Surg. ECF x3

Preop CT/RT + Postop CTECF x2 RT/FuSurg. ECFx3

F. III TOP GEAR (International Intergroup)

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Treatment options in Resectable EGJ Adenocarcinoma


Stahl et al. J Clin Oncol 2009; 27: 851-856

119 Pts in 5 y (planned 177)Siewert I / II-III 55%/45%ECOG 0/1 60%/40%Weight loss >10% 16%

Preop CT/RT PFLx2PE/RTCx

OS (3y) 27% HR 0.67 (0.41-1.07) p 0.07 47%Local Control (3y) 59% HR 0,45 (0,19-1,05) p 0.06 76%

Resectable EGJ adenocarcinomaF. III POET (Preop CT vs Preop CT-RT)


Preop. CTPFLx3Cx

Resectable EGJ AdenocaPhase III POET

Sv

Control Local27.7%

36%

EGJ AdenocarcinomaSiewert Clasification

«Esophageal» options? Preop CT/RT

«Gastric» options? Perioperative CT

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Cetuximab-CT/RT: No metastatic Esophageal CaTwo negative P III… and one recent doubtful P III

1.- Crosby T el al. Lancet Oncology 2013 ; 2.- Suntharalingam et al, ASCO-GI 2014 ; 3.- Ruhstaller T el al, ASCO 2017

258 PTS (P.III no initiated due to futility analysis)

Esophageal Ca (Epid/Aden)St I-III

Cis-Cape/RT4 courses, 3º-4º with 50Gy

Cetuxi+Cis-Cape/RT4 courses, 3º-4º with 50Gy

P. II-III SCOPE 1 1

1º Endpoint P II: TTF (24 w) 66% 77% OS (median) 22,1m HR 1,53; p 0,03 25,4m

More Toxicity in the Cetuximab arm

328 PTS Esophageal Ca(Adenoc 62%)St I-IVA

Cis-Paclitaxel/RT50Gy

Cetuxi+Cis-Pacli/RT50Gy

P.III RTOG 0436 2

1º Endpoint OS (12 m) 64% p 0,7 65% OS (24 m) 44% p 0,7 42%

No differences between Ca epiderm and Adenoca

300 PTS Esophageal Ca(Adenoc 63%)cT3-4 or N+, M0 Cis-DCis/RT SxCet+Cis-DCet-Cis/RTSx Cet

P.III SAKK 75/08 3

1º Endpoint DFS (3y) 45% HR 0.79 p 0,13 41% OS (3y) 62% HR 0.73 p 0,05 49%

Better LocoRegional control with Cet; No differences in distant control

Primary Objetive: Overall Survival

UK MRC ST03 (MAGIC-B) Phase III trial:ECX ± Beva (perioperative) in early stage GC

Gastric or GEJ Cancertype III resectable

N=1063

ECX3 cycles

ECX + Avastin3 cycles

ECX3 cycles

ECX + Avastin3 cycles

SurgeryAvastin

6 cycles

Cunningham et al. , ECC-ESMO 2015

ECX ECX-AvastinPrimary objetive: OS (3 y) 48.9% HR 1.06 p

Studies with trastuzumab in resectable Her2+ esophago-gastric adenocarcinoma

36 PtsResectable Her2 +,Gastric-EGJ

CancerPrimary endpoint: DFS

Perioperative Xelox-Trastuz.Xelox-T x3Surg. Xelox-T x3Tx12

P. II NEOXH (Spain)

53 Pts Resectable Her 2+, Gastric-EGJ

Cancer Primary endpoint: pCR

Perioperative FLOT-Trastuz.FLOT-T x4Surg. FLOT-T x4Tx9

P II AIO-STO 0310 (Germany)

(Hofheinz R et al, ASCO 2014, #4073) R0: 93% , pCR: 22%

(Rivera F et al, ASCO-GI 2015 #107) R0: 78% (MAGIC: 69%)pCR: 8% (MAGIC: 0%)

24 m PFS: 60% (MAGIC: 45%)24 m OS: 75% (MAGIC: 50%)

USO EXPERIMENTAL/FUERA DE INDICACIÓN

Ongoing trials with Inmunotherapy in GC

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Cisplatino-Fluoropirimidina…..¿Carboplatino?…..¿Taxanos?… F III POWER con CF +/- panitumumab

(Negative: ASCO 2017)…En inicio estudios con inmunoterapia

Introducción Tratamiento de la Enfermedad Resecable

Ca. Esofago Adenoca Gástrico Adenoca de la UEG Nuevas dianas

Tratamiento de la Enfermedad Avanzada Ca. Epidermoide de esófago Adenoca del esofago distal, la UEG y gástrico

Quimioterapia Nuevas dianas


Chemotherapy

0 5 10 15

EOX (6)XP (7)

ECX (6)ECF (6)DCF (4)EOF (6)

IF (5)CF (4)

FAMTX (2)BSC (1)

Months

C+S1 (3)

1Murad et al 1993; 2Vanhoefer et al 2000; 3Ajani et al 2009;

4Van Cutsem et al 2006; 5Dank et al 2008; 6Cunningham et al 2008; 7Kang et al 2009;

8Van Cutsem et al 2009

ChemotherapyMedian OS

10-11 m

Introducción Tratamiento de la Enfermedad Resecable

Ca. Esofago Adenoca Gástrico Adenoca de la UEG Nuevas dianas

Tratamiento de la Enfermedad Avanzada Ca. Epidermoide de esófago Adenoca del esofago distal, la UEG y gástrico

Quimioterapia Nuevas dianas


Patogénesis del cáncer“Capacidades” que le permiten al tumor crecer y progresar

Hanahan D, et al. Cell. 2011.

Evasión de supresores de la

proliferación

Evitando la destrucción por la

Inmunidad

Induciendoangiogenesis

Permitiendo la inmortalidad

replicativa

Promoviendola inflamación

Activando la invasión y metástasis

Inestabilidadgenómica y mutaciones

Resistiendo la apoptosis

Desregulación de los mecanismos energéticos

celulares

Señalesproliferativasmantenidas

Emerging Capabilities

Anti-HER2

Inmunoterapia

Antiangiogénicos

Chart1

1st Qtr

2nd Qtr

3rd Qtr

4th Qtr

10

10

10

10

10

10

Sales

10

10

10

10

Sheet1

Sales

1st Qtr10

2nd Qtr10

3rd Qtr10

4th Qtr10

10

10

10

10

10

10

Anti-HER 2Success: TrastuzumabDisappointment: Lapatinib, T-DM1Hopes: Pertuzumab

AntiangiogenicsSuccess: Ramucirumab, ApatinibDisappointment: bevacizumab, sorafenibDeveloping: regorafenib…

InmunotherapyOther biologics

Negative trials: anti-EGFR, everolimus, anti FGFR2, anti-MET/HGF, olaparib

New targeted drugs in Advanced Gastric Cancer

3807 scrined pts 810 HER2+. 584 pts included

97% M1; 32% EGJ; 10% ECOG 2 CX(87%)-/F(13%)-Trast 86mg/kg/3w

P. III TOGA (C-X/F vs C-X/F-Trastuzumab)

CX(87%)/F(13%)

Bang IJ, Lancet 2010

Primary endpoint OS

OS (median) 11.1 m HR 0.74 p 0.004 13.8 mPFS(median) 5.5 m HR 0.71 p 0.0002 6.7 mRR (CR+PR) 34% p 0.001 47%






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P III trials with Lapatinib


OS (median) 8.9 m HR 0,84 p 0.20 11 mpts HER-2 IHQ+++ (preplanned analysis)

(median) 7.6 m HR 0,59 p 0.01 14 m

Asia, 2nd line HER2+. 261 pts Taxol-LapatinibTaxol

P. III TYTAN Yung-Jue Bang et al. ASCO-GI 2013

1st líne, HER2+. 540 pts (Asian 40%) CapOx-LapatinibCapOx

P. III LOGIC ASCO 2013

Primary endpoint OS

- OS (median) 10.5 m HR 0,91 p 0.73 12.2 m No better results in en HER-2 IHC+++ OS improvement in asian and

Gastric Cancer: Other anti HER-2T-DM1

Phase II/III GATSBY T-DM12nd line Taxane345 pts, HER2 + Primary endpoint: P.II: efficacy, tox

P.III: OS

Mechanism of action

USO EXPERIMENTAL/FUERA DE INDICACIÓNKang Y-K et al. ASCO GI San Francisco 2016

Gastric Cancer: Other anti HER-2: Pertuzumab

P III JACOB (NCT01774786) CT-Tratuzumab-Pertuzumab1st line CT-Trastuzumab-placebo780 pts, HER2 + 1º endpoint: OS

Ongoing


Ramucirumab (IgG1 anti VGFR-2)Two positive P III in second line…

1) Fuchs CS et al. Lancet 2014; 383: 31-9

P. III REGARD 1Advanced Gastric Adenoca. , 2nd line 355 pts (rand 2/1)

PlaceboRamucirumab 8 mg/kg cada 2 semOS (median) 5.2 m HR 0,77 p 0,04 3,8 mPFS(median) 2,1 m HR 0,48 p

Ramucirumab (IgG1 anti VGFR-2)Two positive P III in second line …

1) Wilke H et al. Lancet Oncology 2014

P. III RAINBOW 1Advanced Gastric cancer, 2nd line 665 pts (rand 1/1)

Paclitaxel-placebo

Paclitaxel 80 mg/m2 d 1,8,15Ramucirumab 8mg/kg d 1, 15 cada 28d

Primary Endpoint:OS

OS (median) 9,6 m HR 0,80 p 0,01 7,3 mPFS(median) 4,4 m HR 0,63 p

Second line Treatmentin Advanced Gastric Cancer

appropiate for combinedtreatment

ECOG 0-1 ¿2?no appropiate for combined

treatmentno appropiate for

monotherapy

comorbidities, patient preferences

S Qin et al, ASCO 2014, # 4003

VEGFR TKI: Apatinib

P. III chineseAdvanced Gastric Cancer, 3rd line

273 pts

PlaceboApatinibPrimary endpoint: OSOS (median) 6,5 m HR 0,70 p 0,01 4,7 mPFS(median) 2,6 m HR 0,44 p






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774 pts 98% M1; 14% EGJ; 5% ECOG 2intestinal 38%, diffuse 50%, mixt 8%Asia 49%, Europe 32%, America 19% CX-Beva 7,5 mg/kg/3s

P. III AVAGAST (CX vs CX-Bevacizumab)

CX-placebo

Van Cutsem E, ESMO 10 #713P; Kang, ASCO 2010 #LBA4007

OS (median) 10,1 m HR 0,87 p 0.10 12,1mPFS (median) 5.3 m HR 0,80 p 0.003 6,7 m(CR+PR) 37% p 0.03 46%No important differences in G 3-4 Toxicity

1º endpoint: OS

DFS


195 pts (asian), 1st lineM1; 15% EGJ; ECOG 0-1

CX-Sorafenib

P. III STARGATE (CX vs CX-Sorafenib)

CX

Kang YK et al, ESMO 2014 #LBA4007

1º endpoint: DFS

OS

PFS (median) 5,3 m HR 0,92 p 0.60 5,6 mOS (median ) 10,8 m HR 0,93 p 0.66 11,7 m(CR+PR) 52% p 0.82 54%


147 pts , 2nd,3rd line, ECOG 0-1, Rand 2:1Stratification: Region (37% Asia); previous lines (1:43%) Placebo

Rand P. II INTEGRATE (Regorafenib vs placebo)

Regorafenib1600 mg/d, d 1-21 each 28d

1º endpoint: PFSPFS (median) 2,7 m HR 0,41 p

Immunotherapy in Gastric Cancer Immunomodulation Immune “check points”

OtherImmunotherapies

Pembrolizumab (Anti PD-1)

1.- Muro, Lancet Oncol 2016 ; 2.- Fuchs CS et al, ASCO 2017 ; 3.- Bang YJ, et al, ASCO 2017

39 pts PD-L1 + (40% of tested GC pts)RR 22%, DC: 36% (Central Review)Similar activity in asian and no-asian

P I KEYNOTE 012 1 (GC cohort)

P II KEYNOTE 059 2 (Cohort 1: Pembro in GC ≥ 3rd line)259 pts PD-L1 + 57% RR 11%, DC 27% Higher activity in PD-L1+ vs PD-L1- and very hight in MSI (4% of pts)

RR: 15% 6% 57%DC 33% 19% 71%

Dur of Resp 16,3 m 6,9 m

P II KEYNOTE 059 3 (Cohort 2: Pembro-Cis-Fu/Xelo in GC 1st line)25 pts PD-L1 + 64% , RR 60%, DC 80%

Higher activity in PD-L1+ vs PD-L1-RR: 69% 38% DC 81% 75%

P III trials ongoing1st line (KN 062) (PD-L1+) ; CT vs Pembro vs CT+ Pembro2nd line (KN 061) (PD-L1+/-) ; CT vs Pembro

Nivolumab (Anti PD-1)A recently presented positive asian P III in refractory disease

1.- Kang YK, et al. ASCO-GI 2017 . Abst 1

P. III ONO-4538 / BMS-936558 1Advanced Gastric cancer, refractory

to standard therapy (> 2 lines) 493pts (rand 2/1)

PlaceboNivolumab 3 mg/kg / 14 d Primary Endpoint:OS

OS (median) 5.3 m HR 0,63 p< 0,0001 4.1 m12 m 26 % 10 %

PFS(median) 1,6 m HR 0,60 p

Checkmate 032: Nivolumab +/- Ipi• Phase I/II with a GC/GEJ/EC cohort (160 pts) . Irrespectively of PD-L1 status

Janjigian ASCO 2016

Nivo 3 mg/kg Q2WNivo 1 mg/kg + ipi 3 mg/kg Q3WNivo 3 mg/kg + ipi 1 mg/kg Q3W

x 4 cycles Nivo 3 mg/kg Q2W

ORR (1st End Point)

OS PFS

P III Check Mate 649 (1st line advGC)

1266 pts

Primary endpoint OS

50%

20%

22%

9%

TCGA Nature 2014

Ongoing trials with Inmunotherapy in GC

161 pts HER2- and Claudine + (48%) 1st line AGC

EOF/X

Rand P. II FAST (IMAB 362 in 1st line AGC)

IMAB + EOF/X

PFS (median) 7.9 m HR 0,5 p 0.001 5.7 mOS (median ) 13.2 m HR 0,51 p < 0.05 8. 4 m

OS in High claudina HR 0,44

Al-Batran SE et al. ASCO 2016 #4001USO EXPERIMENTAL/FUERA DE INDICACIÓN

1º endpoint: PFSOS

Cetuximab and PanitumumabTwo negative P III: EXPAND and REAL-3


Everolimus (mTOR inhibitor)

1) Ohtsu A, et al. J Clin Oncol, 20132) Al-Batran SE, et al. ASCO-GI 2017. Abst 4

P. III GRANYTE-1 1Advanced Gastric Cancer, 2nd, 3rd line

656 pts

PlaceboEverolimus Primary endpoint: OS

OS (median) 5.4 m p 0,12 4,3 mPFS(median) 1,7 m p

AZD 4547 (anti FGFR2)

1) Bang YJ, et al. ASCO 2015

Rand P. II SHINE 1Advanced Gastric Cancer, 2nd, 3rd line

- FGFR2 polysomy or gene amplification (FISH)

960 pts screened 71 pts included PaclitaxelAZD 4547 Primary endpoint: PFS

PFS (median) 1.5 m 3.5 m


Anti HGF/c-Met in Advanced Gastric CancerP III with Rilotumumab and Onartuzumab

P. III METGASTRIC mFOLFOX-Onartuzumab1st line , c-Met +, HER2 - mFOLFOX-placebo560 pts, Primary endpoint: OS Shah MA, ASCO 2015

P III RILOMET-1 ECX-Rilotumumab (15 mg/kg)1st line , c-Met +, HER2 - ECX-Placebo609 pts, Primary endpoint: OS Cunningham D, ASCO 2015

OS PFS

OS and MetICH

FISH

OS PFS

PFSMet 2+/3+

OSMet 2+/3+

Olaparib (PARP inhibitor)

1) Bang et al. ESMO 2016. # LBA25

P. III GOLD 1Advanced Gastric Cancer, 2nd, 3rd line

525 pts (Asia) (18% ATM – (IHQ)

Placebo

+ Paclitaxel

Olaparib (100mg/12h)

+ Paclitaxel

Co-Primary endpoints: OS (all pts)

OS (ATM- pts) p < 0,025 (Hochberg approach)

OS (median)All pts 8.8 m HR 0.79 p 0,026 6.9 mATM- pts 12 m HR 0.73 p 0,24 10 m


Conclusiones: enfermedad Resecable


Cancer

Gastric Cancer

- Perioperative Chemotherapy- Postoperative Chemo-Radiotherapy- Postoperative Chemotherapy ??


Conclusions: New drugs

Antiangiogenics SUCCESS with Ramucirumab and Apatinib DISAPPOINTMENT:Bevacizumab (advanced / periop.) , Sorafenib

WAITING for Regorafenib Inmunotherapy: A positive P.III. with nivolumab

Waiting for other P III Selection of pts

Anti-HER-2 SUCCESS with Trastuzumab, But negative results with Lapatinib and T-DM1 WAITING for the P III with Pertuzumab

Other Biologics Negative trials: anti-EGFR, everolimus, anti FGFR2, anti-MET/HGF, olaparib

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GRACIAS

Número de diapositiva 1TítuloCáncer Esófago-Gástrico �Grupo heterogéneo de enfermedadesNúmero de diapositiva 4Número de diapositiva 5Número de diapositiva 6TítuloTreatment options in Resectable �-Esophageal Cancer�- EGJ Adenocarcinoma�- Gastric Adenocarcinoma �Treatment options in Resectable �-Esophageal Cancer�- EGJ Adenocarcinoma�- Gastric Adenocarcinoma �� Definitive Chemo-RadiotherapyQT/RT definitiva en C. Esófago Número de diapositiva 12Treatment options in Resectable �-Esophageal Cancer�- EGJ Adenocarcinoma�- Gastric Adenocarcinoma �QT vs QT/RT Preoperatoria en Ca Esófago ��Is it possible to avoid Surgery�after CT/RT? �� Is it possible to avoid Surgery�after CT/RT? � Phase III: FFCD 9102�(Bedenne, J Clin Oncol, 2007) TítuloTreatment options �in Resectable Gastric Cancer� �Treatment options �in Resectable Gastric Cancer� �GASTRIC “Global Advanced/Adjuvant stomach Tumor Research through International Collaboration”��JAMA. 2010 May 5;303(17):1729-37� �� Treatment options �in Resectable Gastric Cancer� �Postoperative Chemo-Radiotherapy�SWOG 9008/INT 0116Número de diapositiva 26Postoperative Chemo-Radiotherapy� Postoperative Chemo-Radiotherapy vs Postop Chemotherapy � Postoperative Chemo-Radiotherapy vs Postop Chemotherapy � Treatment options in Resectable �-Esophageal Cancer�- EGJ Adenocarcinoma�- Gastric Adenocarcinoma �� Perioperative Chemotherapy �MAGIC-1 � �� Perioperative Chemotherapy �P III FLOT4 Should RT be added to perioperative CT? Should RT be added to perioperative CT? TítuloTreatment options in Resectable EGJ Adenocarcinoma� �� Número de diapositiva 39EGJ Adenocarcinoma�Siewert ClasificationTítuloCetuximab-CT/RT: No metastatic Esophageal CaNúmero de diapositiva 43Studies with trastuzumab in resectable Her2+ esophago-gastric adenocarcinoma Número de diapositiva 45Slide 30TítuloNúmero de diapositiva 48Número de diapositiva 49Número de diapositiva 50Patogénesis del cáncer �“Capacidades” que le permiten al tumor crecer y progresarNúmero de diapositiva 52Número de diapositiva 53Número de diapositiva 54Número de diapositiva 55Número de diapositiva 56Número de diapositiva 57Número de diapositiva 58Número de diapositiva 59Número de diapositiva 60Ramucirumab (IgG1 anti VGFR-2) �Two positive P III in second line…Ramucirumab (IgG1 anti VGFR-2) �Two positive P III in second line …Second line Treatment �in Advanced Gastric CancerNúmero de diapositiva 64Número de diapositiva 65Número de diapositiva 66Número de diapositiva 67Número de diapositiva 68Número de diapositiva 69Número de diapositiva 70Número de diapositiva 71Número de diapositiva 72Nivolumab (Anti PD-1) �A recently presented positive asian P III in refractory diseaseCheckmate 032: Nivolumab +/- Ipi P III Check Mate 649 (1st line advGC)Número de diapositiva 76Slide 30Número de diapositiva 78Número de diapositiva 79Número de diapositiva 80Everolimus (mTOR inhibitor)AZD 4547 (anti FGFR2)Número de diapositiva 83Olaparib (PARP inhibitor)Número de diapositiva 85Número de diapositiva 86Número de diapositiva 87

Avances en el Tratamiento del Cáncer Gástrico y Esofágico 11.2.pdf · QT/RT de inducción en CE:...

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