1

Master Class for OncologistsWelcome to

Miami, FL

December 19, 2009

7:30 AM - 8:15 AMSession 1:

Update on Esophagogastric Cancers:Weighing the Therapeutic Options

Peter C. Enzinger, MDDana-Farber Cancer Institute

& Harvard Medical School

Presenter Disclosure Information

The following relationships exist related to this presentation:

• Dr Enzinger serves as a speaker/consultant for sanofi-aventis U.S., Pfizer Inc., Roche, Genentech, and ImClone/Bristol-Myers Squibb.

Off Label/Investigational Discussion:Use of irinotecan, oxaliplatin, and capecitabine for metastatic esophagogastric cancer

Brown LM, et al. J Natl Cancer Inst. 2008; 100:1184-1187.

Incidence of Esophageal Cancer: 16,470 new cases and 14,530 deaths in 2009

++++ > 8-fold risk+++ 4-8-fold risk++ 2-4-fold risk+ < 2-fold risk+/- Conflicting studies--- No proven risk

R isk F a cto r S C C AD C To b acco +++ ++ ETOH +++ --- Barre t t’s Es o p h ag u s --- ++++ W eekly Reflu x Sy mp to ms --- +++ Ob es ity --- ++ Po v erty ++ --- A ch alas ia ++++ Cau s tic in ju ry to es o p h ag u s ++++ --- Ty lo s is (NEPPK) ++++ --- Plu mmer-Vin s o n s y n d ro me ++++ --- His to ry o f h ead & n eck can cer ++++ --- H/o b reas t ca t reated with rad io th erap y +++ ++ Freq u en t co n s u mp tio n o f h o t b ev erag es + --- HPV (Ch in a , Jap an , So u th A frica) +/- --- Beta b lo cker --- + /- A n tich o lin erg ics --- + /- A min o p h y lin es --- + /-

Risk Factors: Esophageal CA

Enzinger PC. N Engl J Med. 2003;349:2241-2252.0

2

4

6

8

10

12

14

16

18

0 20-29 30-39 40 + 0 3.5 11 14.5 25 28.5 36+

AdenocarcinomaSquamous Cell CarcinomaAdenocarcinomaSquamous Cell Carcinoma

Cigarettes per Day Drinks per WeekData from Takezaki 2000, Wu 2001 and Brown 2001

Odds Ratio

Tobacco/Alcohol and Esophageal Cancer

1-19

2

Squamousepithelium Metaplasia

Low-Grade

Dysplasia

High-Grade

DysplasiaADC METS

Oxidative stressInflammation

G1&G2COX-2BCL-2

4%/yr

0.5%/yr1%/yr

5%/yr10%

GERD1:7 Americans

0.005%/yr

Early Genetic Events:17pLOH p53; 9pLOH p16

cyclin D12nd Tier Genetic Events:

p53 mutation; p16 mutation/methylationEGF(R), telomerase RNA

Late Genetic Events:4 N (G2) aneuploidy of 5q/13q

and LOH of 5q/13q(Rb)/18q

?

c-erbB2

E-cadherin-catenin

85+%

Neoplastic Progression of Barrett’s Esophagus 2003 AJCC Classification of Esophageal Carcinoma

AJCC. AJCC Cancer Staging Manual. 6th ed. 2002.

Males in USAFemales in USA

Incidence of Gastric Adenocarcinoma

• No longer a “top ten” cause of cancer death in USA• 2009: 21,130 new cases and 10,620 deaths• Still the 4th leading cause of cancer death in Europe

CA Cancer J Clin ‘09

Risk Factors for Gastric Adenocarcinoma

• Nutritional– Low fat or protein consumption– Salted meat or fish– High nitrate consumption

• Environmental– Poor food preparation (smoked)– Lack of refrigeration– Poor drinking water (well water)– Occupation (rubber, coal workers)– Smoking (1.6x)– Low social class

• Medical– Prior gastric surgery– Helicobacter pylori infection (2x)– Gastric atrophy and gastritis

Helicobacter pylori

N=0mutagens

Higher pH

Bacterial growth + nitrate

Gastric ascorbic acid

B-carotene

Proposed Cascade of Pathologic Events inGastric Adenocarcinoma

Salt

Normal Superficialgastritis

Atrophicgastritis Metaplasia Dysplasia Carcinoma

Salt N-nitroso Chronic inflammationcarcinogens and reactive oxygen species

inhibition

promotion

Adapted from Correa

1997 AJCC Classification of Gastric Carcinoma

AJCC2003

T2a: a tumor that invades the muscularis propriaT2b: a tumor that invades into the subserosa

a/b

a/b

a/b

AJCC. AJCC Cancer Staging Manual. 6th ed. 2002.

3

Which one of the following strategies has NOT been shown in the setting of a randomized trial to extend

survival in a 68 yo man (PS 0, no significant comorbidities) with locally advanced GE junction

adenocarcinoma?

Localized Gastroesophageal Junction Cancer ?

1.1. Chemotherapy Chemotherapy surgery surgery chemoradiationchemoradiation therapytherapy2.2. Chemotherapy Chemotherapy surgery surgery chemotherapychemotherapy3.3. ChemoradiationChemoradiation therapy therapy surgerysurgery4.4. Surgery Surgery chemotherapy chemotherapy chemoradiationchemoradiation chemotherapychemotherapy

What Can Surgery Accomplish?

Localized Esophageal Cancer

Wijnhoven BP, et al. Ann Surg. 2007;245:717-725.

Esophageal Cancer Treated With Surgery

Does Adjuvant Chemotherapy Improve Surgery Outcomes?

Localized Esophageal Cancer

Neoadjuvant Chemotherapy Compared with Surgery Alone for Localized Esophageal Cancer

Thirion. ASCO 2007

FP (*) x 2/3 every 28 days

Resection

Within 4 weeks

4 - 6 weeks

Resection

4 – 6 weeks

FP x 3/4 or no treatment

Follow-up

Randomization

CT + S S

FNLCC ACCORD 07-FFCD 9703 Trial: Schema

(*) FP = 5FU: 800 mg/m² CI x 5 days - CDDP: 100 mg/m² at d1 or d2, 1-hr infusion Boige. ASCO 2007

Stage II-IVA75% distal esophagusor GEJ ADC

4

S CT + S P-valuen = 85 n = 98

Tumor stage

T0 0% 3%T1, T2 32% 39%T3, T4 68% 58% 0.16

Nodal status (%)

N- 20% 33%N+ 80% 67% 0.054

Nb nodes removed

Median 19 19Range (2 - 82) (1 - 49)

Boige. ASCO 2007

ACCORD 07: Pathological Results

713162738537911114172741536593113

0,00

0,20

0,40

0,60

0,80

1,00

0 1 2 3 4 5 6 7A risque

logrank : p = 0,021

___ S___ CT + S

years

ACCORD 07: Overall Survival

At risk

5-year OS: 24% (95% CI, 16%-33%) vs 38% (95% CI, 28%-47%)

Logrank P-value = 0.021Hazard Ratio, 0.69 (95% CI, 0.50-0.95)

Boige. ASCO 2007

Does NeoadjuvantChemoradiation

Therapy Improve Surgery Outcomes?

Localized Esophageal Cancer All-Cause Mortality Estimates for Neoadjuvant C/RT Compared with Surgery Alone

Gebski V, et al. Lancet Oncol. 2007;8:226-234.

POET: Schema

Arm A

Week

Arm B

PLF I PLF III (3 weeks)

15 x 2 Gy in 3 weeks

PE (1 week)

Surgery

Surgery

1 1314 17 20-21

PLF: Cisplatin 50mg/m2, 1h, d 1,15,29. Leukovorin/5-FU 500mg/m2 2h / 2g/m2 24h, d1,8,15,22,29,36PE: Cisplatin 50 mg/m2, 1h, d 2+8. Etoposide 80 mg/m2, 1h, d 3-5

PLF II

6 7

PLF I PLF II

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

POET: Downstaging

Arm A Arm B P-value(n = 49) (n = 45)

Path CR 2% 16% 0.03T1-4N0M0 35% 49%Node neg. 37% 64% 0.01T0-4N+M0 55% 31%T1-4N+M1 8% 4%

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

5

POET: Overall Survival

Log rank P = 0.07

HR Arm B vs A0.67; 95% CI, 0.41-1.07)

Arm B

Arm A

47.4%

27.7%

Arm A Arm B

Median survival 21.1 mo 33.1 mo

Median follow-up 45.2 mo 46.2 moStahl M, et al. J Clin Oncol.2009;27:851-856.

Can Surgery Improve the Outcomes of Chemoradiation?

Localized Esophageal Cancer

Prospective Randomized Intergroup Study:Radiation Therapy vs Chemotherapy + Radiation Therapy

for Localized SCC or ADC of the Esophagus

Schema

tumor size

histology

weight loss

2 x Cisplatin (75 mg/m2) + 5-fluorouracil (1000 mg/m2/d CI x 4d) + radiation therapy (5000 cGy)

R

A

N

D

O

M

I

Z

E

radiation therapy (6400 cGy)

Herskovic A, et al. N Engl J Med. 1992;326:1593-1598.al-Sarraf M, et al. J Clin Oncol. 1997;15:277-284.

Intergroup Study

Herskovic A, et al. N Engl J Med. 1992;326:1593-1598. al-Sarraf M, et al. J Clin Oncol. 1997;15:277-284.

• A total of 455 patients with localized esophageal cancer were given 2 courses of 5-FU/cisplatin plus radiation therapy.

• 259/455 patients experienced a “partial response”, were considered operative candidates, and entered the randomized component of the trial.

Chemoradiation Therapy With or Without Surgery: French Phase III Trial

Bedenne. J Clin Oncol. 2007;25:1160-1168.

Chemoradiation Therapy With or Without Surgery: French Phase III Trial

Survival

3-month mortality median 2-year

5-FU/CDDP x 3 +

1% Radiation

therapy

19.3

months

40%

P=0.56

Surgery 9% 17.7 months

34%

Partial Response

R A N D O M I Z E

(259 pts)

Bedenne. J Clin Oncol. 2007;25:1160-1168.

6

Patients:(N = 177)

uT3-4,N0-1, M0with SCC

Chemoradiation Therapy With or Without Surgery:German Phase III Trial (Schema)

RANDOMIZE

3 cycles:5-FU/LV + Cisplatin + Etoposide

Chemoradiation:Cisplatin+Etoposide

+ 40 Gy RTSurgery

Chemoradiation:Cisplatin+Etoposide

+ > 60 Gy RT

Stahl. J Clin Oncol. 2005;23:2310-2317.

Chemoradiation Therapy With or Without Surgery: German Phase III Trial (Results)

Arm CompletedTreatment

TreatmentMortality

3-yr LocalRecurrence

MedianSurvival

3-Year SurvivalInduction Chemo

All Responder

Arm A:C/RT S 62% 12.8% 41% 16 mo. 31% 54%

Arm B:C/RT 85% 3.5%

(P = 0.03)64%

(P = 0.004)15 mo. 24%

(P = 0.02)54%

Stahl. J Clin Oncol. 2005;23:2310-2317.

C/RT +/- Surgery for Esophageal SCC

Stahl. J Clin Oncol. 2005;23:2310-2317.

Median survival (N=172):Arm A (C/RT S) -16.4 monthsArm B (C/RT only)-14.9 months

31.3% (P = 0.02)

24.4%

Conclusions from these Results

Localized Esophageal

Pre-operative cisplatin/5-FU chemotherapy offers a small survival advantage in distal esophageal and GE junction cancer.

Neoadjuvant cisplatin-based chemoradiation offers a greater survival advantage with better local control but increased surgical morbidity.

Surgery may not be needed in patients who have a clinical response to chemoradiation.

What Can Surgery Accomplish?

Localized Gastric Cancer

Survival in 633 patients, according to 1997 TNM stage

Gastric Cancer Kranenberg. Br. J Cancer 2001

42%

66%

82%

20%

12%

7

5-Year Survival %

Authors n DST TG

Gouzi 1989 169 48 48

Bozzetti 1999 648 64 62

Randomized Controlled Trials

Prospective Studies of Total Gastrectomy (TG) vsSubtotal Gastrectomy (DST) for Distal Gastric Cancer What Is the Ideal Extent of Lymphadenectomy?

D0 - removes less than all relevant N1 nodes

D1 - requires the dissection of the N1 nodes (1 - 6)*

D2 - includes the N1 and N2 nodes (7–11)

D3 – includes the N1, N2, and N3 nodes (12-15)

D4 – includes the N1, N2, N3 and N4 nodes (16)

*nodes 2, 4 remain if distal subtotal gastrectomy

4d6 4d

4d4sb

533

12 4sa

4sb

1616

1616

Japanese Data

Marujama. Semin Oncol 1996

Randomized Study of D1 and D2 Dissection for Gastric Cancer

711 patients undergoing curative resection of gastric cancer

Peri-Op Morbidity

Peri-OpMortality

Median Hospital Stay

(days)5-Year

Survival

11-YearSurvival(P = 0.53)

D1Dissection 25% 4% 14 45% 30%

D2Dissection 43% 10% 16 47% 35%

Bonenkamp JJ, et al. N Engl J Med. 1999;340:908-914.Hartgrink HH, et al. J Clin Oncol. 2004;22:2069-2077.

What are Proven Strategies to Enhance Outcomes for Surgical

Resection?

Localized Gastric Cancer Intergroup Protocol 0116Adjuvant Therapy for Gastric Cancer

Stratify

depth of tumor penetration 5-FU/leucovorin x 1

5-FU/leucovorin +

4500 cGy radiation

5-FU/leucovorin x 2

number involved nodes

location of tumor observation

extent of surgery

R

A

N

D

O

M I

Z

E

Macdonald. N Engl J Med 2001

8

Intergroup Protocol 0116

Macdonald JS, et al. N Engl J Med. 2001;345:725-730.

Chemoradiotherapy

Surgery Only

50%

41%

P = 0.005

3 years

MAGIC Trial: Schema

ECF x 3 q3/523-6 weeks

Resection

ECF x 3 q3/52

6-12 weeks

CSC S

Follow-up

Within 6 weeks

Resection

Cunningham D, et al. N Engl J Med. 2006;355:11-20. 503 Patients:15% Lower Third12% GE Junction

MAGIC: Survival

Patients at risk

Logrank P-value = 0.009Hazard Ratio = 0.75 (95% CI, 0.60 - 0.93)

CSCS

250 168 111 79 52 38 27253 155 80 50 31 18 9

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Months from randomization0 12 24 36 48 60 72

149 250

170 253

Events TotalCSC

S

Sur

viva

l rat

e

36%

23%

50%

41%

Cunningham. N Engl J Med 2006 Which one of the following strategies has NOT been

shown in the setting of a randomized trial to extend survival in a 68 yo man (PS 0, no significant

comorbidities) with locally advanced GE junction adenocarcinoma?

Localized Gastroesophageal Junction Cancer ?

1.1. Chemotherapy Chemotherapy surgery surgery chemoradiationchemoradiation therapytherapy

2.2. Chemotherapy Chemotherapy surgery surgery chemotherapychemotherapy

3.3. ChemoradiationChemoradiation therapy therapy surgerysurgery

4.4. Surgery Surgery chemotherapy chemotherapy chemoradiationchemoradiation chemotherapychemotherapy

Conclusions from these Results

Localized Gastric:

Post-operative 5-FU-based chemoradiation therapy remains the standard of care for muscle-invasive or LN positive disease.

The MAGIC trial demonstrates that pre- and post-operative ECF improves survival. It may be particularly beneficial for downstaging extensive local disease.

What are the Active Agents and Combinations for this Disease?

Metastatic Esophagogastric Cancer

9

Prior to selecting systemic treatment, which of the following molecular studies should be performed on tumor tissue from a 73 yo man with gastric cancer

metastatic to liver and lungs?

Metastatic Esophagogastric Cancer ?

1.1. EGFREGFR2.2. KK--rasras3.3. HERHER--2/neu2/neu4.4. MSIMSI5.5. cc--KITKIT

Advanced Esophagogastric Cancer:Older Single Agents

Class Agent Mechanism Of Action ResponseAntimetabolite 5-Fluorouracil Inhibits thymidylate synthase 21%

Methotrexate Inhibits purine nucleotide and thymidylatesynthesis 11%

Pemetrexed Inhibits thymidylate synthase 21%

Gemcitabine Inhibits ribonucleotide reductase 0%

Antibiotic Mitomycin-C Produces interstrand DNA cross-links 30%

Anthracycline Doxorubicin Intercalates into DNA and interactswith topoisomerase II

17%

Epirubicin 18%

Heavy Metal Cisplatin Produces intrastrand and interstrand DNA cross-links

21%

Carboplatin 9%

TopoisomeraseInhibitor Etoposide Binds to and inhibits topoisomerase II 8%

National Cancer Institute. http://www.cancer.gov/drugdictionary/

Chemotherapy for Advanced Gastric Cancer:Important Randomized Studies

Study Regimen n Response (%) OS (months) P-value

Ohtsu et al. 20031

FCF

UFTM

10510570

11349

7.17.36.0

NS

Vanhoefer et al. 20002

FAMTXELFCF

133132134

129

20

6.77.27.2

NS

Webb et al. 19973ECF

FAMTX111108

4521

8.95.7

0.0009

Ross et al. 20024ECFMCF

289285

4244

9.4 +QOL8.7 -QOL

NS

F = 5FU; A = doxorubicin; M = mitomycin; MTX = methotrexate; C = cisplatin; U = uracil; FT = tegafur;E = etoposide (in ELF) or epirubicin (in ECF); L = leucovorin; NS = not significant.

1. Ohtsu et al. J Clin Oncol. 2003;21:54; 2. Vanhoefer et al. J Clin Oncol. 2000;18:2648;. 3. Webb et al. J ClinOncol. 1997;15:261; 4. Ross et al. J Clin Oncol. 2002;20:1996.

ToGA - Schema

HER2-positiveadvanced GC

(n = 584)

5-FU or capecitabine+ cisplatin(n = 290)

R

aChosen at investigator’s discretion GEJ, gastroesophageal junction

5-FU or capecitabinea

+ cisplatin+ trastuzumab

(n = 294)Stratification factors− advanced vs metastatic − GC vs GEJ− measurable vs non-measurable− ECOG PS 0-1 vs 2− capecitabine vs 5-FU

Phase III, randomized, open-label, international, multicenter study

Van Cutsem. ASCO 2009

3807 patients screened1

810 HER2-positive (22.1%)

0

10

20

30

40

50

60

ToGA: Response Rate

2.4%5.4%

32.1%

41.8%

34.5%

47.3%

Intent to treat

ORR= CR + PR; CR, complete response; PR, partial response

P = 0.0599

P = 0.0145

F+C + trastuzumabF+C

P = 0.0017Patients (%)

CR PR ORR

Van Cutsem. ASCO 2009

ToGA: Overall Survival

Time (months)

294290

277266

246223

209185

173143

147117

11390

9064

7147

5632

4324

3016

2114

137

126

65

40

10

00

No. at risk

11.1 13.8

0.00.10.20.30.40.50.60.70.80.91.0

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

Event

FC + TFC

Events

167182

HR

0.74

95% CI

0.60, 0.91

P-value

0.0046

MedianOS

13.811.1

T= trastuzumab Van Cutsem. ASCO 2009

10

Advanced Esophagogastric Cancer:Newer Agents

Class Agent MOA1 Response2,3

AntimetaboliteCapecitabine Reduces thymidine production and competes with uridine

triphosphate for incorporation into RNA 30%

S-1 Inhibits thymidylate synthase and CDHP, and competes with uridine triphosphate for incorporation into RNA 26%

Heavy Metal Oxaliplatin Produces intrastrand and interstrand platinum-DNA cross-links na

Taxane Paclitaxel Binds to and stabilizes tubulin inhibiting microtubule disassembly

13%

Docetaxel 21%

TopoisomeraseInhibitor Irinotecan Inhibits topoisomerase I 21%

1. National Cancer Institute. http://www.cancer.gov/drugdictionary/;2. Schöffski P. Ann Oncol. 2002;13:13-22. Ajani JA. Oncologist. 2005.10;49-58.

CDHP = 5-chloro-2,4-dihydroxypyridine; na = not available.

REAL-2: Schema

Previously untreated patients

with locally advanced or metastatic

oesophago-gastric cancer

RANDOMISATION

EpirubicinCisplatinFluorouracil

EpirubicinCisplatinXeloda (capecitabine)

EpirubicinOxaliplatinFluorouracil

EpirubicinOxaliplatinXeloda (capecitabine)Stratified for:

- Centre (63 centres mainly UK, 2 Aus) - Locally advanced versus metastatic - PS 0/1 versus 2

2 x 2 design

Cunningham D, et al. N Engl J Med. 2008;358:36-46.

REAL-2: Survival (ITT)

0

20

40

60

80

100

0 1 2 3Time since randomisation (years)

Prob

abili

ty o

f sur

viva

l (%

)

ECF EOF ECX EOX

Arm OS (m) 1-year survival (95% CI)

P-value HR(95% CI)

ECFEOFECXEOX

9.99.39.9

11.2

37.7 (31.8-43.6)40.4 (34.2-46.5)40.8 (34.7-46.9)46.8 (40.4-52.9)

0.6120.3890.020

10.96 (0.79-1.15)0.92 (0.76-1.11)0.80 (0.66-0.97)

Cunningham D, et al. N Engl J Med. 2008;358:36-46.

EOX

ECF

Capecitabine / Cisplatin vs. 5-FU / CisplatinSchema

Previously untreated advanced gastric cancer

XP - Capecitabine 1000/m2 twice daily d1-14 Cisplatin 80/m2 d1 q3 weeks

N=160

N=156

FP - 5-FU 800 mg/m2 d1-5 Cisplatin 80 mg/m2 d1 q3 weeks

Primary endpoint: Non-inferiority in PFS, HR <1.4

Secondary endpoints: Response rate (RR), time to response (TTR), overall survival (OS), safety

R

Kang. ASCO 2006

• ORR: FP (29%) XP (41%)• MS: FP (9.3 mo) XP (10.5 mo)• Toxicity: Similar• Conclusions: XP is non-inferior to FP (HR, 0.8; 95% CI, 0.6-.0)

Kang. ASCO 2006

Estimated probability

XP (n=139) 5.6 (4.9—7.3)FP (n=137) 5.0 (4.2—6.3)

Median PFSMonths (95% Cl)

HR = 0.81 (95% Cl, 0.63—1.04)Compared to HR upper limit 1.25, P = 0.0008

MonthsPer protocol analysis

0 2 4 6 8 10 12 14 16 18 20 22 24 26

1.0

0.8

0.6

0.4

0.2

0.0

Capecitabine/Cisplatin vs 5-FU/CisplatinProgression-Free Survival

5-FU/LV + Oxaliplatin vs 5-FU/LV + CisplatinSchema

Previously untreated advanced gastric cancer

FLO - 5-FU 2600 mg/m2 24-hr CILeucovorin 200 mg/m2

Oxaliplatin 85 mg/m2 d1q2 w

N = 112

N = 106

FLP - 5-FU 2000 mg/m2 24-hr Leucovorin 200 mg/m2

q1 wCisplatin 50 mg/m2 d1q2 w

Primary endpoint: Superiority for TTP

Secondary endpoints: Response rate (RR), time to treatment failure (TTF), overall survival (OS), safety

R

Al-Batran SE, et al. J Clin Oncol. 2008;26:1435-1442.

11

• ORR: FLO (34%) FLP (27%); improved safety profile for FLO• Conclusions: Primary endpoint not met and survival data are pending

FLO FLPMedian TTP (months) 5.7 3.8TTP Events 80 (71.4%) 81 (76.4%)

HR, 0.8 (95% Cl, 0.58 - 1.09)

Log rank P = 0.081Wilcoxon P = 0.0179

Monthsn at riskn at risk

FLOFLP

Prob

abili

ty (%

)

1.0

0.8

0.6

0.4

0.2

0.0

0 5 10 15 20 25 30

102 52 15 4106 35 13 5

5-FU/LV + Oxaliplatin vs 5-FU/LV + CisplatinTime to Progression

Al-Batran. J Clin Oncol 2008

Irinotecan/Cisplatin–Based Tx for Esophagogastric Cancer

Author Regimen Cancer Type

# Patients Major Response

Rate

G3-4 Diarrhea

G4 ANC

Median Survival

Ilson. 1999

weekly Esoph. GE jct.

35 57% 11% 9% 14.6 mo.

Ajani. 2002

weekly GE jct. Gastric

38 58% 22% 15% 9 mo.

Ajani. 2002

weekly GE jct. Gastric

29 pretreated

31% 13% 9% 5 mo.

Satoh. 2002

weekly Gastric. 15 naive 25 pretx

53% 20%

3% 10% 9.9 mo.9.0 mo.

Enzinger.2009

weekly EsophGastric

3125

67%37%

26% 11% 14.3 mo.9 mo.

TPC: docetaxel – cisplatin - irinotecan

PC: cisplatin - irinotecan

Prior to selecting systemic treatment, which of the following molecular studies should be performed on tumor tissue from a 73 yo man with gastric cancer

metastatic to liver and lungs?

Metastatic Esophagogastric Cancer ?

1.1. EGFREGFR2.2. KK--rasras3.3. HERHER--2/neu2/neu4.4. MSIMSI5.5. cc--KITKIT

Conclusions from these Results

Metastatic Esophagogastric:

The most active single agents are the 5-fluoro-pyrimidines, platinum analogues, taxanes, and irinotecan.

Combinations of fluoropyrimidine and platinum remain the standard of care. Trastuzumab should be added for HER2/neu 2-3+ or FISH+ tumors.

Weekly irinotecan/cisplatin is most convenient. FOLFOX is best for patients with hepatic or renal insufficiency.

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Questions & Answers

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