Challenging Cases in Cancer: Integration of Findings from ASCO 2007 Gastric Cancers

Challenging Cases in Cancer: Integration of Findings from ASCO 2007

Gastric Cancers

David H. Ilson, MD, PhDAssociate Attending Physician

GI Oncology Service

Memorial Sloan-Kettering Cancer Center

New York, NY

Upper GI Cancer: US Incidence in 2007

• 93,150 new cases gastric, esophageal, pancreatic, hepatobiliary cancer– 8% of new cancers

– 81% fatality rate

– 15% of American cancer deaths

• Decline in gastric cancer incidence

• Increase in esophageal , GE JX, cardia adeno

• Increase in hepatocellular Ca

Jemal et al, CA Cancer J Clin 57: 43-66; 2007

Gastric Cancer: Current Therapy

• Adjuvant– Post op 5-FU/LV + RT: increases 5-yr OS by 10% (U.S.

Standard, INT 116)

– Pre and Post op ECF: increases 5-yr OS by 13% (U.K. Standard, MAGIC trial)

Case 1: GE Junction Adenocarcinoma

• A 79-year-old male presents with increasing dysphagia, 15 pound weight loss, odynophagia

• Past history: NIDDM, BPH, hypercholesterolemia

• EUS: T3N1 adenocarcinoma, 50% circumferential

• CT scan: distal esophageal mass

• PET scan: uptake in the primary, SUV

• The patient is admitted from clinic for complete dysphagia, and has endoscopy and Polyflex stent placement


PET scan CT scan

Which treatment option would you recommend? Esophagectomy Preop chemotherapy with ECF followed by

esophagectomy and post op ECF Preop combined chemoradiotherapy followed by

surgery Primary combined chemoradiotherapy without

surgery


Case 1: GE Junction Adenocarcinoma• The patient received induction chemo with

weekly carboplatin and paclitaxel for 3 treatments.

• Dysphagia improved post stent and with chemotherapy

• PET scan: response to induction chemo (SUV 9.7 5.3), EGD: response, stent was removed

• Combined chemotherapy with weekly carbo/paclitaxel and RT 5040 cGy was administered

• EGD post therapy x 2 (4 and 8 weeks after RT): treatment related stricture dilated, biopsy negative

• Repeat PET scan 2 months post RT: SUV further reduced, 3.1

• Surgery deferred

PET 1 PET 2

PET 3


GE Junction and Esophageal Cancer: Adjuvant Therapy

• Survival with surgery alone: 20-40%

• Adjuvant trials in esophageal cancer have evaluated preop therapy – Preop Chemotherapy

– Preop Chemo + radiotherapy

» Most common U.S. practice

Esophageal Cancer: Preop Chemotherapy

• Negative Trials

• U.S. INT 113

– 3 pre, 3 post op cycles of 5-FU + Cisplatin

– 440 pts

– Adeno 54%, Squamous 46%

– No improvement in R0 resection rate, disease free or overall survival

– Path CR 2.5%

0

20

40

60

80

100

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Kelsen et al, NEJM 339: 1979; 1998

Esophageal Cancer: Preop Chemotherapy

• Positive trials

• U.K. MRC OEO-2

– 2 preop cycles of 5-FU + Cisplatin

– 802 pts

– Adeno 66%, Squamous 31%

– 6% increase in R0 resection rate, 9% increase in 2-year OS

– Path CR 4%

• U.K. MAGIC: pre and post op ECF in gastric cancer

– 25% of 500 pts had GE junction or distal esophageal adeno

– No improvement in R0 resection rate, 13% increase in 5-year OS

– No Path CRs

MRC Lancet 359: 1727; 2002, Cunningham NEJM 355: 11; 2006

Esophageal Cancer: Consensus on Adjuvant Therapy

• Something more than surgery alone should be done• Adenocarcinoma

– Preoperative chemotherapy improves overall survival» MAGIC: 13% improvement at 5 yr» MRC 0E0-2: 9% improvement at 2 yr

– No clear impact on rate of R0 resection

• Addition of RT to chemotherapy– Improves rates of curative resection in some trials– Achieves pathologic complete responses in 10-30%– Phase III trials: only 2 of 5 recent trials showed a survival

benefit for preop chemo + RT

MRC Lancet 359: 1727; 2002, Cunningham NEJM 355: 11; 2006

Preop Chemo in Esophageal and Gastric Cancer: FFCD / FNLCC

Preop CT (2-3 cycles)(N = 98) 89%

Surgery(N = 109) 96%

Postop CT(N = 145)

S(N = 111)

Surgery(N = 110) 99%

CT + S(N = 113)

CT = 5-FU + Cisplatin

Boige, et al. ASCO 2007. Abstract 4510

Surgical and Pathological Results

S

N = 110

CT = S

N = 109No. pts (%)

Extent of resection

No. resection 10 (9) 7 (6)

R0 81 (74) 95 (87) P = 0.04

R1 6 (5) 4 (4)

R2 12 (11) 2 (2)

RX 1 (1) 1 (1)


Overall Survival

5-year DFS: 24% (16 - 33%) vs. 38% (28 - 47%)


Disease-free Survival


5-year DFS: 21% (14 - 30%) vs. 34% (26 - 44%)

Preop Chemotherapy in Esophageal Adenocarcinoma

• Survival benefit for preop chemotherapy with CF (cisplatin and 5-FU)

• 14% improvement in 5-yr OS, HR 0.69– Similar to survival for gastric cancer in MAGIC trial

• 13% rate of improvement in R0 resection rate

• Impact on tumor downstaging: not statistically significant



• Major impact was reduction in systemic recurrence– Systemic: 56% for surgery 42% for chemo + surgery

– Local: 26% for surgery = 24% for chemo + surgery

• Similar results for CF compared to ECF-MAGIC– Epirubicin may not be needed

• Role of epirubicin?– OEO-05 (U.K. MRC)

– Preop ECF vs. CF in esophageal cancer



• Preop Chemo in esophageal and GE JX adeno improves survival

• Relative small sample 224 pts, differences of 10-15% come down to outcomes in only 10-15 patients

• Preoperative staging– EUS not performed

– Accuracy of pre-therapy stage ?

– No stratification for stage


Individual Patient Data-based Meta-analysis Assessing Pre-operative Chemotherapy in Resectable

Oesophageal Carcinoma

• Individual patient data from preop chemo trials (esophageal squamous and adenocarcinoma)

• 9 trials OS (2102 pts)

• 7 trials DFS (1849 pts)

• 2 dominant trials: – U.S. INT 113 (467 pts)

– U.K. MRC OEO-2 (802 pts)

• Slightly more than 50% of patients had squamous ca

• Preop Chemo: Overall survival improvement with a HR of 0.87 (P = 0.0033)– Translates into 4.3% improvement in OS at 5-yrs

Thirion P, et al. ASCO 2007. Abstract 4512

Primary End-point: Overall Survival

Patients at risk

Control 1054 321 144 74 38 20Chemo pre-op 1047 361 153 90 52 31

Su

rviv

al

0.0

0.2

0.4

0.6

0.8

1.0

Time (years)

0 2 4 6 8 10

Absolute benefit at 5 years:4.3 %

Patients at risk


Su

rviv

al

0.0

0.2

0.4

0.6

0.8

1.0

Time (years)

0 2 4 6 8 10

Absolute benefit at 5 years:4.3 %


Secondary End-point: DFS

Patients at risk


Dis

easefr

ees

urv

ival

0.0

0.2

0.4

0.6

0.8

1.0

Time (years)

0 2 4 6 8 10

Absolute benefitat 5 years:4.1 %

Patients at risk


Dis

easefr

ees

urv

ival

0.0

0.2

0.4

0.6

0.8

1.0

Time (years)

0 2 4 6 8 10

Absolute benefitat 5 years:4.1 %


Individual Patient Data-based Meta-analysis Assessing Pre-operative Chemotherapy in Resectable

Oesophageal Carcinoma

• Although overall survival benefit independent of histology– Adeno: 20% 27%

– Squamous: 16% 20%

• Other endpoints:– R0 resection rate improved by 5%

– Post Operative Mortality: not increased with preop chemo

• Conclusions: Preop chemotherapy– Modest improvement in 5-yr OS (4.3%)

– Greater effect for adenocarcinoma then squamous cell carcinoma of the esophagus


Preoperative Chemotherapy (CTX) Versus Preoperative Chemoradiotherapy (CRTX) In Locally Advanced Esophagogastric Adenocarcinomas: First

Results of A Randomized Phase III Trial

M. Stahl, M. K. Walz, M. Stuschke, N. Lehmann, M. H. Seegenschmiedt, J. Riera Knorrenschild, P. Langer, M.

Bieker, A. Königsrainer, W. Budach, H. Wilke

Abstract 4511

Stahl M, et al. ASCO 2007. Abstract 4511

Patients with locally advanced esophagogastric

adenocarcinomaCisplatin 50 mg/m2

Etoposide 80 mg/m2

Radiation 30 Gyfor 3 wks

Arm A(N = 60)

Arm B(N = 60)

Cisplatin 50 mg/m2

Folinic Acid 500 mg/m2

5-FU 2 g/m2

for 2.5 courses

Cisplatin 50 mg/m2

Folinic Acid 500 mg/m2

5-FU 2 g/m2

for 2 courses

Trial Design

Results at Surgery

CTX

(N = 59)

CRTX

(N = 60)

Patients with S 88.1 % 81.7 %

R0-resection 69.5 % 71.7 %

R1/R2 13.6 % 3.3 %

Exploration (N) 3 4

Peritoneal mets. 2

Unresected 1

Peritoneal mets. 3

Hepatic mets. 1


Pathohistologic Results

CTX(N = 49)

CRTX(N = 45)

P

T0N0M0 2.0 % 15.6 % 0.03

T1-4N0M0 34.7 % 48.9 %

T0-4N0M0 36.7 % 64.4 % 0.01

T0-4N+M0 55.1 % 31.1 %

T0-4N+M1 8.2 % 4.4 %


Mortality After Surgery

CTX(N = 52)

CRTX(N = 49)

Hospital mortality 2 (3.8 %) 5 (10.2 %)

Pneumonia 1 2

Anastom. leakage 1 2

Cardiac shock 0 1

Fisher’s exact P = 0.26


Overall Survival

Log rankP = .07HR arm B vs. A: 0.67 (0.41-1.07)

Follow-up: 45.6 mos


Years

Su

rviv

al D

istr

ibu

tio

n F

un

ctio

n

0

0.25

0.50

0.75

1.00

0 1 3 52 4 6

CRTX

CTX 27.7%

47.4%

Freedom from Local Tumor Progression

Log rankP = 0.06HR arm B vs. A: 0.45 (0.19 -1.05)

Years

Su

rviv

al D

istr

ibu

tio

n F

un

ctio

n

0

0.25

0.50

0.75

1.00

0 1 3 52 4 6

CRTX

CTX

76.5%

59.0%


Preop Chemo vs. Preop Chemo RT

• Preop Chemo and Preop Chemo RT are feasible

• No difference in rate of R0 resection, + RT

• Higher post op mortality, + RT in multi institution trial

• Strong trend favoring improved OS, + RT– 20% at 3 years (P = 0.07)

• Strong trend favoring improved local PFS, + RT– 18% at 3 years (P = 0.06)


Preop Chemo vs. Preop Chemo RT

• Cannot conclude that the addition of RT improves outcome– Trial underpowered for primary endpoint

• Further trials of pre and post op chemo ± RT are warranted

• Netherlands: CRITICS Trial– Preop ECX Surgery – Post op chemo ± RT

• Korea:– Preop Capecitabine + Cisplatin Surgery – Cape/Cis ± RT


Gastric/Esophageal Cancer: Current Therapy

• Gastric Cancer:– Metastatic: 5-FU + cisplatin, RR of 20%, Med S 8-9 mos

» Epirubicin (ECF), docetaxel + CF (DCF):

• 35-40% RR, med survival 9 mos

» Capecitabine, oxaliplatin = CIV 5-FU, cisplatin

Gastric Cancer Chemotherapy: What Regimen to Use?

• Docetaxel + CF > CF: toxicity• Irinotecan + CIV 5-FU = CF: less toxicity• Oxaliplatin + Capecitabine: non inferior• Doublets: Platin: + Irinotecan or Taxane or Fluor

Flour: + Irinotecan or Taxane or Platin

Oxaliplatin EOX or EOF

Cape ECX or EOX

XP FLO FUFIRI DCF ECF

Pts 489 513 160 109 170 221 126

%,RR 44% 45% 41% 34% 32% 36% 45%

TTP, mos -- -- 5.6 5.5 5.0 5.6 NS

OS, mos 10.9 10.4 10.5 -- 9.0 9.2 8.9


• A 50-year-old man presents with increasing solid food dysphagia and a 20 pound weight loss.

• EGD reveals a GE junction mass with a biopsy revealing adenocarcinoma.

• A CT scan reveals multiple hepatic mets, lung and adrenal mets.

• Past history is only noted for asthma.

• PS 0.

CT Scan PET Scan


Which treatment option would you recommend? Single agent 5-FU or capecitabine 5-FU/Cisplatin or FOLFOX ECF, ECX, or EOX DCF: Docetaxel, 5-FU, Cisplatin FOLFIRI Irinotecan + Cisplatin


• Phase III trials indicate that ECF is superior to FAMTX, and that DCF is superior to CF

• The patient was treated on a phase II trial of modified DCF– Docetaxel 40 mg/m2 day 1

– Bolus 5-FU 400 mg/m2, Leucovorin 400 mg/m2 day 1, followed by 5-FU 1000 mg/m2/day x 2 days

– Cisplatin 40 mg/m2 day 3

– Cycled every 2 weeks

– + Bevacizumab 10 mg/kg day 1

• Scans every 6 weeks showed progressive response, dysphagia resolved, PET scan normalized in the liver

• Dose reductions of 5-FU and docetaxel for mucositis

• No significant neutropenia or diarrhea

• Patient continues on therapy at 6 months


CT Scan 2

CT Scan 1

PET Scan 2PET Scan 1

Gastric / Esophageal Cancer Abstracts: ASCO 2007

• Metastatic disease: gastric cancer– S-1 vs. S-1 + Irinotecan

– S-1 vs. 5-FU vs. 5-FU/Cisplatin

– S-1 vs. S-1/Cisplatin

– DCF vs. Docetaxel + Capecitabine

S-1

• S-1: novel oral fluorouracil formulation

• FT: Tegafur, 5-FU prodrug +

• CDHP: DPD inhibitor +

• Oxo: bowel protectant

• Molar ratio of 1.0: 0.4: 1.0

• Developed as orally absorbed 5-FU preparation with potentially less bowel toxicity

S-1

• CDHP: inhibits DPD, which degrades 5-FU– 180-fold higher DPD inhibitory activity than Uracil

• A high blood level of 5-FU retained when CDHP is combined with FT

• CDHP enhances oral FT uptake by blocking degradation by DPD in the bowel

S-1

• Oxo: orotate phosphoribosyltransferase inhibitor

• Oxo: inhibits conversion of FT to FU in the bowel

• Reducing GI toxicity

S-1: Mechanism of Action

Irinotecan Plus S-1 (IRIS) Versus S-1 Alone as First-line Treatment for Advanced Gastric Cancer: Preliminary

Results of a Randomized Phase III Study

• S-1 vs. S-1 + Irinotecan – 326 pts

– RR 27% vs. 42% (P = 0.035)

– Grade 3/4 neutropenia: 9% vs. 27%

– Grade 3/4 diarrhea: 6% vs. 16%

– OS pending (powered to detect 3.5 mos inc OS)

Chin K, et al. ASCO 2007. Abstract 4525

Randomized Phase III Study of 5-fluorouracil (5-FU) Alone Versus Combination of Irinotecan and Cisplatin (CP) Versus S-1 Alone In

Advanced Gastric Cancer (JCOG9912)

• S-1 vs. CIV 5-FU vs. irinotecan/cisplatin 704 pts, primary endpoint irinotecan arm: increase 1-yr OS by 10%– Grade 3/4 neutropenia, nausea, diarrhea

» 65% for IC vs. 1-5% for S-1 or 5-FU



– RR: IC: 38% 5-FU: 9% S-1: 28%

– PFS: 4.8 mos 2.9 mos 4.2 mos

– OS 12.3 mos 10.8 mos 11.4 mos

• Irinotecan/cisplatin and S-1 are superior to 5-FU, S-1 single agent approaches combination therapy activity

Boku, et al. ASCO 2007. Abstract LBA4513

Randomized Phase III Study of S-1 Alone Versus S-1 + Cisplatin In the Treatment for Advanced Gastric Cancer (The SPIRITS trial)

SPIRITS

• S-1 vs. S-1 + Cisplatin

• S-1 40-60 mg BID x 3 weeks alone, vs. S-1 + Cisplatin 60 mg/m2 day 8, 2 weeks rest

• Primary endpoint OS: 8 mos 12 mos, 284 pts

• S-1: Active single agent, superior to CIV 5-FU alone

• Combination + cisplatin superior

• S-1 + Cisplatin a new standard in Japan

• FLAGS: Western trial of 5-FU vs. S-1 + Cisplatin

S-1S-1 +

CisplatinP

Number 150 148

RR 31% 54% 0.0018

OS11

mos13 mos 0.0366

1-year 47% 54%

2-year 15% 24%

PFS 4 mos 6 mos 0.0089

Grade 3/4 Neut

11% 40%

Grae 3/4 Diarrhea

3% 3%

Grade 3/4 Nausea

1% 12%Narahara et al. ASCO 2007. Abstract 4514

Weekly Docetaxel-based Chemotherapy Combinations in Advanced Esophago-gastric Cancer

• DCF in gastric cancer: 35% RR, TTP 5.6 mos, OS 9.2 mos

– 82% grade 3/4 neut., 30% neut. fever, 20% diarr and stomatitis

• Phase II:

– DCF: Doc 30 mg/m2 day 1 and 8, 5-FU 200 mg/m2/day x 21 days, Cisplatin 60 mg/m2 day 1 vs.

– DX: Doc 30 mg/m2 day 1 and 8, Cape 1200 mg/m2/day x 14 days

DCF DX

50 56

RR 49% 26%

Febrile

Neutro4% 2%

Gr 3/4

Diar10% 7%

Gr 3/4

Stomat 22% 2%

PFS 5.9 mos 4.2 mos

OS 12.8 mos 10.1 mos

Tebbutt et al. ASCO 2007. Abstract 4528

Challenging Cases in Cancer: Integration of Findings from ASCO 2007

Pancreatic Cancer

Pancreatic Cancer: Current Therapy

• Primary Disease: Surgical Resection:– Only curative option

» <20-30% operable

» 5 yr survival 0-20%

– Adjuvant:

» Chemo + RT: post op 5-FU/XRT (U.S)

» Chemo Alone: 5-FU + leucovorin (Europe, ESPAC trial), or Gemcitabine alone (Europe, CONKO trial)

• Metastatic Disease:– Gemcitabine 1000 mg/m2/wk, 30 minute infusion

» RR 6%, median survival 5.6 mos, 1-yr survival 18%

– Gem + second drug: negative phase III trials for 5-FU, cisplatin, irinotecan, oxaliplatin, capecitabine

– Gem + Erlotinib increases 1-year survival

– ECOG: Gemcitabine FDR = Gemcitabine FDR + Oxaliplatin (10% RR, med. Surv. 6 months)

Case 3: Pancreatic Adenocarcinoma

• A 56 year old man with worsening diabetic control presents with abdominal pain and a 20 pound weight loss

• A CT scan reveals a pancreatic mass and innumerable hepatic metastases,

• Liver biopsy reveals pancreatic adenocarcinoma

• Past history is notable for now insulin dependent diabetes, hypertension, peptic ulcer disease and hypercholesterolemia.

• PS is 0


Which treatment option would you recommend? Gemcitabine Gemcitabine by fixed dose rate infusion Gemcitabine + erlotinib Gemcitabine + capecitabine Gemcitabine + cisplatin/oxaliplatin


• The patient was treated with gemcitabine (FDR) and oxaliplatin every 2 weeks.

• His CT scans showed substantial response and he gained weight.

• After 4 months doses were reduced due to thrombocytopenia.

• Erlotinib was added at 6 months

• Oxaliplatin was reduced to every 3rd cycle at 8 months, although neuropathy remains grade 1.

• The patient continues on therapy at 22 months.


CT Baseline CT 3 months CT 22 months

Pancreatic Cancer Abstracts: ASCO 2007

• Metastatic Disease, Phase III– Meta Analysis: gemcitabine vs. gem combination chemo

– Second Line: 5-FU vs. 5-FU/oxaliplatin

– SWOG S0205: gemcitabine ± cetuximab

– CALGB 80303: gemcitabine ± bevacizumab

Gemcitabine vs. Gemcitabine + Another Drug?

HR

SurvivalP-Value N

Gem + platinum 0.85 0.01 623, 5 trials

Gem + 5-FU 0.90 0.03 901, 6 trials

Good PS 90%+

Poor PS 60- 80%

0.76

1.08

<0.0001

0.04

1,108, 5 trials

574

Patients with good performance status benefit from Gemcitabine combination chemotherapy: Gem + 5-FU/Cape, or Gem + platinum agent. For poor PS, single agent Gem ± erlotinib

Heinemann , et al. ASCO 2007. Abstract 4515

CONKO-003Phase III 5-FU+FA+Ox vs. 5-FU+FA, Second-line

• Primary endpoint: 2 month improvement in OS

– Patients with POD on Gemcitabine

• Secondary: TTP, RR, toxicity

NTTP

(N = 145)

OS(N = 130)

5-FU+FA+Ox 76 12.3 weeks(10.9 – 123.7)

45 weeks(40.5 – 49.5)

5-FU+FA 89 8 weeks(6.4- 9.5)

35.6 weeks(29.6 – 41.5)

P > 0.05

Riess , et al. ASCO 2007. Abstract 4517

SWOG S0205: Study Schema

Stratify

Locally advanced vs. metastatic

Prior pancreatectomyYes vs. No

Performance status0/1 vs. 2

Gemcitabine +

Cetuximab

Gemcitabine +

Cetuximab

GemcitabineGemcitabine

RANDOMIZE

RANDOMIZE

Philip et al. ASCO 2007. Abstract LBA4509

S0205: Study Objectives

• Primary– Overall survival

• Secondary– Time to treatment failure

– Objective response

– Pain and quality of life (QoL)

– Toxicity

– EGFR expression and its correlation with outcome


S0205: Patient Characteristics

Gem + Cetux

(N = 366)

Gem

(N = 369)

Median Age (years) 63.7 64.3

Female 49% 46%

Performance Status 0/1 87% 87%

Locally Advanced 21% 22%

Measurable Disease 86.3% 88.3%

Prior Pancreatectomy 10% 11%


S0205 Primary Endpoint:Survival of all Patients

5.96.4

HR = 1.09 (95% CI: 0.93, 1.27)

Overall Survival by Treatment Arm

0%

20%

40%

60%

80%

100%

0 12 24 36Months After Registration

Gemcitabine

Gemcitabine and Cetuximab

N369366

Events338331

Median in Months

P = 0.14


S0205: Progression-free Survival

HR = 1.13 (95% CI: 0.97, 1.31)

Progression-free Survival by Treatment Arm

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30Months After Registration

3.0

3.5

Gemcitabine

Gemcitabine and Cetuximab

N369

366

Events360

351

Median in Months

P = 0.058


S0205: Objective Tumor Response

ResponseGem + Cetux

(%)

(N = 316)

Gem (%)

(N = 326)

CR 0 1

PR 12 13

SD 38 30

CR + PR + SD 50 44

PD 40 47


Advanced Pancreatic

CancerN = 590

Gemcitabine Placebo

GemcitabineBevacizumab

Stratification:• Performance status: 0/1 vs. 2• Extent of disease: metastatic vs. locally advanced• Prior radiation: yes/no

RANDOMIZE

CALGB 80303: Trial Design

Kindler et al. ASCO 2007. Abstract 4508

CALGB 80303: Endpoints

Primary Endpoint:

• Overall survival

Secondary Endpoints:

• Objective response rate

• Duration of response

• Progression-free survival

• Toxicity


Patient Characteristics

Characteristic

GemcitabineBevacizumab

(N = 302)

GemcitabinePlacebo

(N = 300)Median age (years) 63.8 65.0MaleFemale

58%42%

51%49%

Performance status 012

36%53%11%

39%52%9%

Locally advancedMetastatic

15%85%

16%84%

Prior radiation 11% 11%


CALGB 80303: Objective Response

Gemcitabine

Bevacizumab

Gemcitabine

Placebo

Complete

Response1% 2%

Partial

Response10% 8%

Stable

Disease36% 31%

Disease Control:

CR + PR + SD47% 40%


CALGB 80303: Progression-free Survival by Treatment Arm

HR=1.00

p=0.99

0 5 10 15 20 25

Months from Study Entry

0.0

0.2

0.4

0.6

0.8

1.0

Pro

po

rtio

n S

urv

ivin

g

BevacizumabPlacebo

Bevacizumab 4.9 mos

Placebo 4.7 mos

HR = 1.00

P = 0.99


CALGB 80303: Overall Survival by Treatment Arm

0 5 10 15 20 25

Months from Study Entry

0.0

0.2

0.4

0.6

0.8

1.0

Pro

po

rtio

n S

urv

ivin

g

BevacizumabPlacebo

Bevacizumab 5.8 mos

Placebo 6.1 mos

HR = 1.03

P = 0.78


Conclusions

• Preoperative chemotherapy and preoperative chemoradiotherapy for adjuvant treatment of GE junction adenocarcinoma

• Potential benefit with the addition of radiation to preoperative chemotherapy with improvements in overall survival and local disease control

• Advanced metastatic gastric cancer – new oral drug S1 has promising activity as a single agent and significant activity in combination with either irinotecan or cisplatin

• Modified DCF regimen has improved toxicity profile in the treatment of advanced metastatic gastric cancer

• Important meta-analysis indicates gemcitabine combination therapy with either a 5-FU or a platinum agent maybe used in pancreatic cancer patients with good performance status

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Challenging Cases in Cancer: Integration of Findings from ASCO 2007 Gastric Cancers

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