A trial of the

National Cancer Institute of Canada Clinical Trials Group

(NCIC CTG)

and the

Australasian Gastro-Intestinal Trials Group(AGITG)

Randomized Phase III Trial of Randomized Phase III Trial of Cetuximab + Best Supportive Care Cetuximab + Best Supportive Care (BSC) versus BSC Alone in Patients (BSC) versus BSC Alone in Patients

with Pre-treated with Pre-treated Metastatic EGFR-Positive Colorectal Metastatic EGFR-Positive Colorectal

Cancer Cancer (NCIC CTG CO.17)(NCIC CTG CO.17)

NCIC CTG CO.17 Abstract Authors

NCIC CTGNCIC CTG• Derek Jonker, M.D.Derek Jonker, M.D.

• Chris O’Callaghan, D.V.M. Chris O’Callaghan, D.V.M. Ph.D. Ph.D.

• Dongsheng Tu, Ph.D.Dongsheng Tu, Ph.D.

• Scott Berry, M.D.Scott Berry, M.D.

• Sheryl Koski, M.D.Sheryl Koski, M.D.

• Marianne Krahn, M.D.Marianne Krahn, M.D.

• Malcolm Moore, M.D.Malcolm Moore, M.D.

AGITGAGITG

• Christos Karapetis, M.D.Christos Karapetis, M.D.

• Niall Tebbutt, M.D.Niall Tebbutt, M.D.

• Guy van Hazel, M.B.B.SGuy van Hazel, M.B.B.S

• R. John Simes, M.D.R. John Simes, M.D.

• John Zalcberg, M.D., John Zalcberg, M.D., Ph.DPh.D

Disclosures

AuthorAuthor EmploymenEmploymentt

Consultant /Consultant /AdvisorAdvisor

Stock Stock OwnerOwner

HonorariaHonoraria

N. TebbuttN. Tebbutt Merck/Merck/AmgenAmgen

Merck/AmgenMerck/Amgen

J. ZalcbergJ. Zalcberg AmgenAmgen

D. JonkerD. Jonker No Conflicts of InterestNo Conflicts of Interest

C. KarapetisC. Karapetis No Conflicts of InterestNo Conflicts of Interest

M. MooreM. Moore No Conflicts of InterestNo Conflicts of Interest

S. BerryS. Berry No Conflicts of InterestNo Conflicts of Interest

S. KoskiS. Koski No Conflicts of InterestNo Conflicts of Interest

M. KrahnM. Krahn No Conflicts of InterestNo Conflicts of Interest

J. SimesJ. Simes No Conflicts of InterestNo Conflicts of Interest

D. TuD. Tu No Conflicts of InterestNo Conflicts of Interest

G. Van HazelG. Van Hazel No Conflicts of InterestNo Conflicts of Interest

C. C. O’CallaghanO’Callaghan

No Conflicts of InterestNo Conflicts of Interest

Study supported by Bristol-Myers-Squibb Company and ImClone Systems Inc.Study supported by Bristol-Myers-Squibb Company and ImClone Systems Inc.

Cetuximab: Multiple Mechanisms of Action

• IgG1 monoclonal IgG1 monoclonal antibodyantibody

• Binds to EGFR and Binds to EGFR and competitively inhibits competitively inhibits ligand binding (e.g. EGF)ligand binding (e.g. EGF)

• Blocks receptor Blocks receptor dimerization, tyrosine dimerization, tyrosine kinase phosphorylation, kinase phosphorylation, and signal transductionand signal transduction

• IgG1-induced Antibody-IgG1-induced Antibody-Dependent Cell Dependent Cell

CytotoxicityCytotoxicity (ADCC) (ADCC)Harari P. Harari P. Clin Cancer ResClin Cancer Res. . 2004;10:428.2004;10:428.

CetuximabEGFR

IgG1 MAb ADCC

IgG1 IgG1 (cetuximab)(cetuximab)

Lysis of antibody-coated cell

MAXIMIZE ANTI-TUMOUR ACTIVITY

EGFR MEDIATED EGFR MEDIATED Anti-tumour Anti-tumour

ActivityActivity

IgG1 MEDIATED IgG1 MEDIATED ADCCADCC

Fan Z, et al. Fan Z, et al. Cancer ResCancer Res.1993;53:4322-8 .1993;53:4322-8

Cetuximab: IgG1-Induced Antibody-Dependent Cell Cytotoxicity

(ADCC)

Cetuximab: Phase II Clinical Data

StudyStudy TreatmentTreatment NN EfficacyEfficacy

ORRORR TTPTTP

Irinotecan FailureIrinotecan FailureCunningham D. Cunningham D. N Eng J N Eng J MedMed 2004 2004(EMR 007 / BOND)(EMR 007 / BOND)

CetuximabCetuximab 111111 10.8%10.8% 1.5 mo1.5 mo

Cetuximab + Cetuximab +

IrinotecanIrinotecan

218218 22.9%22.9% 4.1 mo4.1 mo

Saltz L.Saltz L.J Clin Oncol J Clin Oncol 2004 2004 (IMC 0141)(IMC 0141)

CetuximabCetuximab 5757 8.8%8.8% 1.4 mo1.4 mo

Irinotecan, Oxaliplatin, Fluoropyrimidine FailureIrinotecan, Oxaliplatin, Fluoropyrimidine Failure

Lenz H-J.Lenz H-J.J Clin OncolJ Clin Oncol 2006 2006 (IMC 0144)(IMC 0144)

CetuximabCetuximab 346346 12.4%12.4% 1.4 mo1.4 mo

NCIC CTG CO.17: Randomized Phase III Trial in mCRC

EGFR EGFR testing testing

by IHCby IHC

* Cetuximab 400 mg/m* Cetuximab 400 mg/m2 2 IV week 1 then 250 mg/m IV week 1 then 250 mg/m22 IV weekly IV weekly

Disease Disease Progression Progression

oror

Unacceptable Unacceptable ToxicityToxicity

Stratification:Stratification:• CentreCentre• ECOG PS (0 or 1 ECOG PS (0 or 1 vs.vs. 2) 2)

RREEGGIISSTTEERR

RRAANNDDOOMMI I ZZEE

1:11:1

Cetuximab* + BSC

BSC alone

Failed or intolerant to all recommended therapiesFailed or intolerant to all recommended therapies

NCIC CTG CO.17: EGFR IHC testing – Dako pharmDxTM

• Graded by area of highest intensity 0 to 3+Graded by area of highest intensity 0 to 3+

• Considered EGFR detectable (positive) if any stained cellsConsidered EGFR detectable (positive) if any stained cells

mouse anti-EGFR primary Abmouse anti-EGFR primary Ab

goat anti-mouse secondary Ab labeled goat anti-mouse secondary Ab labeled with with horesradish peroxidasehoresradish peroxidase

EGFREGFR

DAB (colour)DAB (colour)

NCIC CTG CO.17: Study Endpoints*

• Primary: Overall Survival Primary: Overall Survival

• SecondarySecondary– Progression Free SurvivalProgression Free Survival

– Objective Response Rate (RECIST criteria)Objective Response Rate (RECIST criteria)

– Safety Safety

– Quality of Life (to be reported later in Quality of Life (to be reported later in 2007)2007)

* All primary and secondary analyses ITT (except * All primary and secondary analyses ITT (except safety)safety)

NCIC CTG CO.17: Key Eligibility Criteria

• Inclusion CriteriaInclusion Criteria

– Histologically proven EGFR detectable (by IHC) mCRCHistologically proven EGFR detectable (by IHC) mCRC

– ECOG performance status 0, 1 or 2ECOG performance status 0, 1 or 2

– Prior anti-TS therapyPrior anti-TS therapy

– Prior irinotecan or oxaliplatin therapyPrior irinotecan or oxaliplatin therapy

• Failed for metastastic disease orFailed for metastastic disease or

• Relapsed within 6 months orRelapsed within 6 months or

• Documented as unsuitable for therapyDocumented as unsuitable for therapy

• Exclusion CriteriaExclusion Criteria

– Prior therapy with an EGFR inhibitor Prior therapy with an EGFR inhibitor

NCIC CTG CO.17: Statistical Considerations

• Survival Analysis / Sample SizeSurvival Analysis / Sample Size– Two-sided alpha of 5%Two-sided alpha of 5%

– 90% power to detect:90% power to detect:

• 9.6% difference in 1-year survival 9.6% difference in 1-year survival

• hazard ratio [HR] of 0.74 hazard ratio [HR] of 0.74

• assuming a 14.1% 1-year survival for the BSC assuming a 14.1% 1-year survival for the BSC groupgroup

– 445 deaths needed445 deaths needed

• The analysis was conducted after 572 The analysis was conducted after 572 subjects were randomized and 456 deaths subjects were randomized and 456 deaths were recordedwere recorded

NCIC CTG CO.17: Subject DispositionRegisteredRegisteredN = 1243*N = 1243*

RandomizedRandomizedN = 572N = 572

CetuximabCetuximabN = 287N = 287

BSCBSCN = 285N = 285

On TreatmentOn TreatmentN = 17N = 17

On TreatmentOn TreatmentN = 0N = 0

Off TreatmentOff TreatmentN = 271N = 271

Off TreatmentOff TreatmentN = 274N = 274

EGFR detectable; N = 981 (79%)EGFR detectable; N = 981 (79%)

* Patients were allowed to be enrolled at the time of previous chemotherapy * Patients were allowed to be enrolled at the time of previous chemotherapy

Clinical Cut OffClinical Cut Off

• Deaths (N = 12)Deaths (N = 12)• PD (N = 205)PD (N = 205)• Symptomatic progression (N = 27)Symptomatic progression (N = 27)• Drug toxicity (N = 9)Drug toxicity (N = 9)• Subject request (N = 10)Subject request (N = 10)

TreatedTreatedN = 288N = 288

TreatedTreatedN = 274N = 274

No CetuximabNo Cetuximab N = 4N = 4

Withdrew ConsentWithdrew Consent N = 6N = 6N = 5N = 5

NCIC CTG CO.17: Demographic Characteristics

All Randomized PatientsAll Randomized Patients Cetuximab + BSC Cetuximab + BSC

N = 287 (%)N = 287 (%)

BSC BSC

N = 285 (%)N = 285 (%)

GENDERGENDER MaleMale 64.864.8 63.963.9

FemaleFemale35.235.2 36.136.1

AGE (years)AGE (years) MedianMedian 6363 6464

RangeRange 28.6 - 88.128.6 - 88.1 28.7 - 85.928.7 - 85.9

<65 years<65 years 61.761.7 55.455.4

>> 65 years 65 years 38.338.3 44.644.6

ECOG ECOG Performance Performance

StatusStatus

00 25.125.1 22.522.5

11 51.651.6 54.054.0

22 23.323.3 23.523.5

NCIC CTG CO.17: Prior Chemotherapies

Number of Prior Number of Prior Chemotherapy Chemotherapy RegimensRegimens

Cetuximab + Cetuximab + BSCBSC

N = 287 (%)N = 287 (%)

BSCBSC

N = 285 (%)N = 285 (%)

1 - 21 - 2 17.417.4 18.918.9

3 - 43 - 4 68.268.2 63.263.2

≥≥ 55 14.414.4 17.917.9

Type of RegimenType of Regimen

Prior TS InhibitorPrior TS Inhibitor 100.0100.0 100.0100.0

Prior Irinotecan Prior Irinotecan RegimenRegimen

96.596.5 95.895.8

Prior Oxaliplatin Prior Oxaliplatin RegimenRegimen

97.997.9 97.597.5

NCIC CTG CO.17: Overall Survival

Cetuximab + BSCCetuximab + BSC BSCBSC

NN 287287 285285

Median Survival Median Survival (Months) (Months) (95% CI)(95% CI)

6.1 6.1 (5.4, 6.7) (5.4, 6.7)

4.6 4.6 (4.2, 4.9) (4.2, 4.9)

6 Month Survival Rate 6 Month Survival Rate

(95% CI)(95% CI)0.50 0.50

(0.45, 0.56) (0.45, 0.56)0.33 0.33 (0.28, 0.39) (0.28, 0.39)

12 Month Survival Rate 12 Month Survival Rate

(95% CI)(95% CI)0.21 0.21

(0.16, 0.27)(0.16, 0.27)0.16 0.16 (0.11, 0.21) (0.11, 0.21)

Hazard Ratio*Hazard Ratio* 0.770.77

95% CI95% CI (0.64, 0.92) (0.64, 0.92)

Log-Rank*Log-Rank* p-value = p-value = 0.0046 0.0046

* Stratified by ECOG PS (0-1 versus 2) at randomization* Stratified by ECOG PS (0-1 versus 2) at randomization

CETUXIMAB + BSCCENSORED

BSCCENSORED

SUBJECTS AT RISK

CET+BSC 287 217 136 78 37 14 4 0 0 0

BSC 285 197 85 44 26 12 8 2 1 0

Pro

po

rtio

n A

live

Pro

po

rtio

n A

live

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

MONTHS

0 3 6 9 12 15 18 21 24 27

NCIC CTG CO.17: Overall Survival

HR 0.77HR 0.77 (95% CI =0.64 – 0.92) (95% CI =0.64 – 0.92)

Stratified log rankStratified log rank p-value = 0.0046 p-value = 0.0046

Study armStudy arm MS MS (months)(months)

95% CI95% CI

Cetuximab + Cetuximab + BSCBSC

6.16.1 5.4 – 6.75.4 – 6.7

BSC aloneBSC alone 4.64.6 4.2 – 4.94.2 – 4.9

NCIC CTG CO.17: Survival Result by Subgroups

SubsetSubset Hazard Ratio and 95% CI Hazard Ratio and 95% CI

Median SurvivalMedian Survival

CetuxCetux BSCBSC

0.77 (0.64 – 0.92)0.77 (0.64 – 0.92) 6.1 mo6.1 mo 4.6 mo4.6 mo

0.72 (0.58 – 0.89)0.72 (0.58 – 0.89) 7.1 mo7.1 mo 5.0 mo5.0 mo

0.89 (0.62 – 1.27)0.89 (0.62 – 1.27) 3.4 mo3.4 mo 3.0 mo3.0 mo

0.77 (0.61 – 0.98)0.77 (0.61 – 0.98) 6.1 mo6.1 mo 4.6 mo4.6 mo

0.75 (0.56 – 1.00)0.75 (0.56 – 1.00) 5.9 mo5.9 mo 4.5 mo4.5 mo

0.69 (0.50 – 0.94)0.69 (0.50 – 0.94) 5.5 mo5.5 mo 4.2 mo4.2 mo

0.80 (0.63 – 1.01)0.80 (0.63 – 1.01) 6.5 mo6.5 mo 4.8 mo4.8 mo

All randomizedAll randomized

ECOG 0-1ECOG 0-1

ECOG 2ECOG 2

Age <65Age <65

Age Age ≤≤6565

FemaleFemale

MaleMale

Favours BSCFavours BSC

0.40.4 0.60.6 0.80.8

Favours CetuximabFavours Cetuximab

1.21.2 1.41.4 1.61.6

NCIC CTG CO.17: Progression Free Survival

Cetuximab + Cetuximab + BSCBSC BSCBSC

NN 287287 285285

2 Month PF Survival Rate2 Month PF Survival Rate

(95% CI)(95% CI)0.45 0.45

(0.40, 0.51) (0.40, 0.51)

0.39 0.39 (0.33, 0.45) (0.33, 0.45)

4 Month PF Survival Rate 4 Month PF Survival Rate

(95% CI)(95% CI)0.28 0.28 (0.23, 0.33) (0.23, 0.33)

0.13 0.13 (0.09, 0.18) (0.09, 0.18)

6 Month PF Survival Rate6 Month PF Survival Rate (95% CI) (95% CI)

0.15 0.15 (0.10, 0.19) (0.10, 0.19)

0.03 0.03 (0.01, 0.06) (0.01, 0.06)

Hazard Ratio*Hazard Ratio* 0.680.68

95% CI95% CI (0.57, 0.80) (0.57, 0.80)

Log-Rank*Log-Rank* p-value < 0.0001 p-value < 0.0001

* Stratified by ECOG PS (0-1 versus 2) at randomization* Stratified by ECOG PS (0-1 versus 2) at randomization

NCIC CTG CO.17: Progression Free Survival

CETUXIMAB + BSCCETUXIMAB + BSCCENSOREDCENSORED

BSCBSCCENSOREDCENSORED

Pro

po

rtio

n P

rog

ress

ion

-Fre

eP

rop

ort

ion

Pro

gre

ssio

n-F

ree

0.00.0

0.10.1

0.20.2

0.30.3

0.40.4

0.50.5

0.60.6

0.70.7

0.80.8

0.90.9

1.01.0

MONTHSMONTHS

00 33 66 99 1212 1515

HR 0.68HR 0.68 (95% CI =0.57 – 0.80) (95% CI =0.57 – 0.80)

Stratified log rankStratified log rank p-value < 0.0001 p-value < 0.0001

Study armStudy arm Med PFS Med PFS (months)(months)

95% CI95% CI

Cetuximab + BSCCetuximab + BSC 1.91.9 1.8 – 1.8 – 2.12.1

BSC aloneBSC alone 1.81.8 1.8 – 1.8 – 1.91.9

NCIC CTG CO.17: Overall Best ResponseCetuximab + BSC Cetuximab + BSC

N = 287 (%)N = 287 (%)

BSCBSC

N = 285 (%)N = 285 (%)

Partial Response Partial Response 19 (6.6)*19 (6.6)* 0 0

Stable DiseaseStable Disease 84 (29.3)*84 (29.3)* 29 (10.2)*29 (10.2)*

Progressive DiseaseProgressive Disease 133 (46.3)133 (46.3) 155 (54.4)155 (54.4)

Inevaluable for Response Inevaluable for Response 35 (12.2)35 (12.2) 98 (34.4)98 (34.4)

Unknown Unknown 16 (5.6)16 (5.6) 3 ( 1.1)3 ( 1.1)

Objective Response Rate Objective Response Rate (ORR)(ORR) (95% CI) (95% CI)

6.6%*6.6%*

(4.0, 10.2)(4.0, 10.2)

0%0%

Disease Control RateDisease Control Rate 35.9%35.9% 10.2%10.2%

* 4 Cetuximab patients with PR and 6 with SD, and 2 BSC patients with SD were * 4 Cetuximab patients with PR and 6 with SD, and 2 BSC patients with SD were still active atstill active at data cut-off and not included (censored) in data above for “best” responsedata cut-off and not included (censored) in data above for “best” response

Difference in ORRDifference in ORR

(95% CI)(95% CI)

6.6%6.6%

(4.0, 10.2)(4.0, 10.2)

CMHCMH p-value < p-value < 0.0001 0.0001

NCIC CTG CO17: Unplanned Anti-Cancer Therapy*

Cetuximab + Cetuximab + BSCBSC

N = 287 (%)N = 287 (%)

BSCBSC

N = 285 (%)N = 285 (%)

Patients with any anti-Patients with any anti-cancer treatment cancer treatment beforebefore progression progression

4 (1.4)4 (1.4) 45 (15.4)45 (15.4)

RadiotherapyRadiotherapy 2 (0.7)2 (0.7) 24 (8.4)24 (8.4)

ChemotherapyChemotherapy 1 (0.3)1 (0.3) 20 (7.0)20 (7.0)

Hormonal therapyHormonal therapy 0 (0.0)0 (0.0) 4 (1.4)4 (1.4)

ImmunotherapyImmunotherapy 0 (0.0)0 (0.0) 4 (1.4)4 (1.4)

OtherOther 1 (0.3)1 (0.3) 9 (3.2)9 (3.2)

* Not allowed per protocol* Not allowed per protocol

NCIC CTG CO.17: Specific Therapies Before Progression*

Number of PatientsNumber of Patients

Cetuximab + Cetuximab + BSCBSC BSCBSC

TS InhibitorsTS Inhibitors 11 88

Mitomycin-CMitomycin-C 00 44

OxaliplatinOxaliplatin 00 11

IrinotecanIrinotecan 11 77

CetuximabCetuximab 00 66

VEGF InhibitorsVEGF Inhibitors 00 33

* Not allowed per protocol* Not allowed per protocol

NCIC CTG CO17: Therapy Post-Progression

Cetuximab + Cetuximab + BSCBSC

N = 287 (%) N = 287 (%)

BSCBSC

N = 285 (%)N = 285 (%)

Patients with any anti-Patients with any anti-cancer treatmentcancer treatment afterafter progressionprogression

79 (27.5)79 (27.5) 66 (23.2)66 (23.2)

RadiotherapyRadiotherapy 52 (18.1)52 (18.1) 41 (14.4)41 (14.4)

ChemotherapyChemotherapy 36 (12.5)36 (12.5) 38 (13.3)38 (13.3)

Hormonal therapyHormonal therapy 6 (2.1)6 (2.1) 9 (3.2)9 (3.2)

ImmunotherapyImmunotherapy 5 (1.7) 5 (1.7) 11 (3.9)11 (3.9)

OtherOther 13 (4.5)13 (4.5) 13 (4.6)13 (4.6)

NCIC CTG CO.17: Specific Post-Progression Anti-Cancer

TherapiesNumber of PatientsNumber of Patients

Cetuximab + Cetuximab + BSCBSC BSCBSC

TS InhibitorsTS Inhibitors 2424 2020

IrinotecanIrinotecan 1111 1313

Mitomycin-CMitomycin-C 12 12 88

CetuximabCetuximab 11 1616

Oxaliplatin Oxaliplatin 99 55

VEGF InhibitorsVEGF Inhibitors 1010 66

NCIC CTG CO.17: Grade 3 / 4 Adverse Events

Grade 3 / 4 AE Grade 3 / 4 AE

> 10%> 10%

Cetuximab + Cetuximab + BSC BSC N = 288 N = 288

(%)(%)

BSCBSC

N = 274 (%)N = 274 (%)P ValueP Value

Any Grade 3 / 4 AEAny Grade 3 / 4 AE 226 (78.5)226 (78.5) 162 (59.1) 162 (59.1) <0.000<0.00011

FatigueFatigue 95 (33.0)95 (33.0) 71(25.9)71(25.9)

DyspneaDyspnea 47 (16.3)47 (16.3) 34 (12.4)34 (12.4)

Abdominal PainAbdominal Pain 38 (13.2) 38 (13.2) 43 (15.7)43 (15.7)

Pain-OtherPain-Other 43 (14.9) 43 (14.9) 20 (7.3)20 (7.3) 0.0050.005

Infection w/o Infection w/o NeutropeniaNeutropenia 37 (12.8)37 (12.8) 15 (5.5)15 (5.5) 0.0030.003

Rash / Rash / DesquamationDesquamation 34 (11.8) 34 (11.8) 1 (0.4)1 (0.4) <0.000<0.000

11

* Hypomagnesemia as a laboratory toxicity was not correlated to clinical symptoms/ AEs* Hypomagnesemia as a laboratory toxicity was not correlated to clinical symptoms/ AEs

Other Grade 3 / 4 ToxicityOther Grade 3 / 4 Toxicity

Hypomagnesemia*Hypomagnesemia* 15 (5.8)15 (5.8) 00 <0.0001<0.0001

Hypersensitivity Hypersensitivity Reaction Reaction 13 (4.5)13 (4.5) 00 <0.0001<0.0001

Grade 0 Grade 1 Grade 2+

Su

rviv

al

Pro

bab

ilit

y

0

20

40

60

80

100

Survival (months)0 6 12 18

NCIC CTG CO17: OS by Worst Grade of Rash

GradeGrade nnMedian Median SurvivaSurviva

ll

00 3232 2.6 mo2.6 mo

11 111155

4.8 mo4.8 mo

2+2+ 131366

8.4 mo8.4 moPro

port

ion

Aliv

ePro

port

ion

Aliv

e

MonthsMonths- Landmark-type analysis excluding all patients dying within 28 days - Landmark-type analysis excluding all patients dying within 28 days of entryof entry- 90% experienced rash by 29 days, Median time to rash = 10 days- 90% experienced rash by 29 days, Median time to rash = 10 days

GradeGrade HRHR 95%CI95%CI p-valuep-value

2+ 2+ vsvs 0 0 0.330.33 (0.22, (0.22, 0.50)0.50)

<0.0001<0.0001

1 1 vsvs 0 0 0.610.61 (0.40, (0.40, 0.93)0.93)

0.0210.021

2+ 2+ vsvs 1 1 0.540.54 (0.41, (0.41, 0.72)0.72)

<0.0001<0.0001

NCIC CTG CO.17: Conclusions

• Cetuximab significantly prolonged OS compared to Cetuximab significantly prolonged OS compared to BSC in patients in which all other therapy had failedBSC in patients in which all other therapy had failed

• This is the first time single-agent biologic targeted This is the first time single-agent biologic targeted therapy has shown a survival benefit in colorectal therapy has shown a survival benefit in colorectal cancercancer

• PFS and RR were also significantly improved with PFS and RR were also significantly improved with cetuximab over BSCcetuximab over BSC

• The safety profile of cetuximab monotherapy is The safety profile of cetuximab monotherapy is acceptable and consistent with the reported incidence acceptable and consistent with the reported incidence from previous mono-therapy studiesfrom previous mono-therapy studies

• The results of this study add to the large body of The results of this study add to the large body of evidence suggesting benefit for cetuximab in evidence suggesting benefit for cetuximab in metastatic colorectal cancermetastatic colorectal cancer

Acknowledgements

• NCIC CTG and AGITG Investigators and NCIC CTG and AGITG Investigators and Central Office StaffCentral Office Staff

• BMS / ImCloneBMS / ImClone

• Study Nurses, Coordinators, MonitorsStudy Nurses, Coordinators, Monitors

• Patients and their FamiliesPatients and their Families