Www.OncologyEducation.ca Defining the Role of EGFR Monoclonal Antibody Therapy in Metastatic...

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Defining the Role of EGFR Monoclonal Antibody Therapy in

Metastatic Colorectal Cancer

Author: Dr. Phil BedardDate Posted: December 12, 2007


Objectives

• Review the rationale for targeting EGFR in metastatic colorectal cancer therapy

• Outline the differences between the monoclonal antibodies against EGFR

• Understand the common toxicities associated with EGFR monoclonal antibodies

• Summarize the evidence supporting the use of EGFR monoclonal antibody therapy in the first-, second-, and third-line treatment of metastatic CRC

• Discuss possible methods of selection of patients most likely to benefit from EGFR monoclonal antibody blockade with metastatic CRC


Epidermal Growth Factor Receptor (EGFR)

• Member of the epidermal growth factor receptor tyrosine kinase family

• Ligand binding to extracellular domain leads to activation of intracellular signaling cascade, including Akt and MAPK

• Results in proliferation, angiogenesis, increased cell motility, and resistance to chemotherapy


EGFR in Colorectal Cancer

• Expressed in 60-80% CRC– Risk factor for poor prognosis

• Monoclonal antibodies (mAb) demonstrate activity as single agents and in combination with chemotherapy in CRC

• To date, there is no proof that small molecular tyrosine kinase inhibitors (TKIs) are of benefit– CRC lacks EGFR mutations that have been

asssociated with response to TKIs in other disease sites

Townsley CA Br J Cancer 2006Rothernberg ML JCO 2005


Monoclonal AntibodiesAgainst EGFR

• For treatment of metastatic colorectal cancer:– Cetuximab approved by Health Canada and

FDA– Panitumumab approved by FDA


Comparison: Cetuximab vs Panitumumab

Cetuximab Panitumumab

Backbone Chimeric Human

Class IgG1 IgG2

Half-life 5-7.5 days 7.5 days

Loading Dose Yes No

Dosing Schedule

Qweekly Qweekly

Q2weekly

Premedication H1-antagonist None


First-line Therapy:Cetuximab + Chemotherapy


CRYSTAL Trial

Van Custem E Proc ASCO 2007

RANDOMI ZE

1:11:1

FOLFIRI + CetuximabN=648

FOLFIRIN=650

10 Endpoint= PFS

N=1198EGFR expression

via 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


Grade 3/4 EventsFOLFIRI+

Cetuximab (%)

FOLFIRI

(%)

Febrile Neutropenia 2.7 2.2

Diarrhea 15.2 10.5

Vomiting 4.5 5.0

Fatigue 5.0 4.5

Skin Reactions 18.7 0.2

Infusion Related Reactions

2.3 0

Hypomagnesemia

(only available for 20% of patients)

1.8 0.2

Toxicity


Efficacy

Grade 3/4 toxicityFOLFIRI + Cetuximab

N = 648 (%)

FOLFIRI

N = 650 (%)

Response Rate 47 39

Median PFS 8.9 8.0

1 yr PFS 34 23

Median OS NR NR

HR = 0.85 (0.73-0.99); p=0.048

p=0.0038


PFS by Skin Reaction:FOLFIRI + Cetuximab

Skin Reaction Median PFS

Grade 1 5.4 months

Grade 2 9.4 months

Grade 3 11.3 months

* No Grade 4 Reaction Reported* No Grade 4 Reaction Reported


OPUS: Phase II

RANDOMI ZE

1:11:1

FOLFOX + CetuximabN=170

FOLFOXN=168

N=338EGFR+

Metasatic CRC

* 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


Toxicity

Grade 3/4 events

FOLFOX+ Cetuximab

FOLFOX

Neutropenia 27.6 31.5

Diarrhea 7.1 6.0

Fatigue 3.5 3.0

Neurotoxicity 3.5 6.0

Acne-like skin rash

14.1 0


Efficacy

FOLFOX+ Cetuximab

FOLFOX

Response Rate 45.6% 35.7%

* No Survival Data Reported* No Survival Data Reported


Response Rate by Skin Rash

FOLFOX+ Cetuximab

Grade 0 13.0%

Grade 1 42.2%

Grade 2 53.2%

Grade 3-4 66.4%


SWOG 80203

Venook A Proc ASCO 2006

RANDOMI ZE

1:11:1

FOLFOX + Cetuximab

REGISTER

FOLFOXInv choice

FOLFIRIInv choice

FOLFOX alone

FOLFIRI + Cetuximab

FOLFIRI aloneN=258

Metastatic Colorectal CANo EGFR expression required

10 Endpoint= OS


SWOG 80203

• Planned sample size N=2200

• Trial stopped early January 2005 because of poor accrual– Publication of Hurwitz data with IFL +

Bevacizumab (NEJM 2004)

• Data reported with median F/U 16 months


Efficacy

Cetuximab+

FOLFIRI

FOLFIRI Cetuximab+FOLFOX

FOLFOX

Response

CR + PR

44% 36% 60% 40%

Stable Disease

32% 38% 26% 30%

Median PFS

(95% CI)

10.6 mos

(6.2-14.1)

8.4 mos

(6.5-10.3)

8.2 mos

(7.0-12.7)

9.8 mos

(8.3-12.4)


Toxicity

Grade 3/4 Cetuximab+

FOLFIRI

FOLFIRI Cetuximab+FOLFOX

FOLFOX

Diarrhea 22% 15% 14% 10%

Neutropenia 34% 27% 38% 36%


Efficacy: Cetuximabversus Chemotherapy Alone

Cetuximab+CT CT alone

Response Rate 52% 38%

Median PFS

(95%CI)

8.5 mos

(7.0-12.5)

9.4 mos

(8.2-10.8)

Median OS

(95%CI)

16.9 mos

(15.9-?)

?

(17.9-?)


Medical Research Council: COIN Trial (Ongoing)

RANDOMI ZE

1:1:11:1:1

FOLFOX/CapeOX until progression/intolerance

FOLFOX/CapeOX + Cetuximab until

progression/intolerance

N=2421 (Target)No EGFR testing

10 Endpoint= OS

FOLFOX/CapeOXx12 weeks“Stop & Go” Strategy


First-line Therapy:Panitumumab + Chemotherapy


PRIME Trial: Ongoing

Expected Completion: March 2010Expected Completion: March 2010

RANDOMI ZE

1:11:1

Panitumumab + FOLFOX

FOLFOX alone

N=900 (Target Accrual)Metastatic Colorectal CA

No EGFR testing

10 Endpoint= PFS


First-line Therapy:Ceutximab + Chemotherapy +

anti-VEGF


CALGB/SWOG 80405: Ongoing

RANDOMI ZE

1:1:11:1:1

FOLFOX or FOLFIRI + Bevacizumab + Cetuximab

FOLFOX or FOLFIRI + Cetuximab

N=2300 (Target)Metastatic Colorectal CA

No EGFR testing

10 Endpoint= OS

FOLFOX or FOLFIRI + Bevacizumab


Dutch Colorectal Cancer Group CAIRO-2: Ongoing

Expected Completion: December 2007Expected Completion: December 2007

RANDOMI ZE

1:11:1

CapeOX + Bevacizumab + Ceutximab

CapeOX + Bevacizumab

N=750 (Target Accrual)Metastatic Colorectal CA

No EGFR testing10 Endpoint=

PFS & Toxicity


Preliminary Toxicity Data

Grade 3/4 Adverse Events

CAPOX-Bev+

Cetuximab

CAPOX-Bev

Hand-Foot Syndrome

13% 12%

Diarrhea 23% 17%

Febrile Neutropenia

0% 1%

Acne-like Rash 20% 0%

Death <60days 3% 3%


First-line Therapy:Panitumumab + Chemotherapy +

anti-VEGF


Panitumumab Advanced Colorectal Cancer Evaluation (PACCE)

RANDOMI ZE

1:11:1

Panitumumab + Oxali-CT + Bevacizumab

REGISTER

Oxali-based CT(ie FOLFOX)Inv choice

Iri-based CT(ie FOLFIRI)Inv choice

Oxali-CT + Bevacizumab

Panitumumab + Iri-CT + Bevacizumab

Iri-CT + Bevacizumab

Hecht JR GI World Congress 2007


PACCE

• Trial stopped early after interim analysis suggested excess toxicity and inferior efficacy in treatment arm


ToxicityPmab+ Bev/Ox

N=401

Bev/Ox

N=392

Gr 3 (%) Gr 4 (%) Gr 3 (%) Gr 4 (%)

Skin 33 <1 1 0

Diarrhea 21 2 12 1

Dehydration 14 2 4 1

Hypokalemia 8 2 3 1

Hypomagnesemia 3 1 0 0

Neutropenia 12 10 17 7

Neuropathy 9 <1 26 <1

Nausea 10 0 4 <1

Infection 16 2 7 2

DVT 6 0 7 0

PE 0 6 0 4


Efficacy

Pmab+Bev/Ox Bev/Ox Pmab+Bev/Iri Bev/Iri

Response 39% 41% 38% 31%

CR 0% 0% <1% 0%

PR 39% 40% 38% 31%

Median PFS

9.0 mos 10.5 mos ----- -----

Median OS

18.6 mos Not reached ----- -----

HR = 1.29 (1.05-1.58)

HR = 1.44 (1.10-1.88)


Summary: First Line

• CRYSTAL trial suggests that Cetuximab can be safely combined with FOLFIRI in first line setting, with very modest lengthening of PFS of uncertain clinical importance

• PACCE trial demonstrates significant added toxicity with combination of chemotherapy, anti-VEGF therapy and Panitimumab– Similar toxicity not reported with CAIRO-2 trial using

chemotherapy, anti-VEGF therapy and Cetuximab

• Data presently do not support routine use of EGFR mAb therapy in combination with chemotherapy +/- anti-VEGF therapy in first-line setting


Second-line Therapy:Cetuximab + Chemotherapy


Erbitux Plus Irinotecan in Colorectal Cancer (EPIC)

RANDOMI ZE

1:11:1

Cetuximab + IrinotecanN=648

Irinotecan aloneN=650

Prior OxaliplatinChemotherapyEGFR+ (IHC)

Sobrero AF AACR 2007

Cetuximab 400mg/m2 week 1; then 250mg/m2 weekly 400mg/m2 week 1; then 250mg/m2 weekly

Irinotecan 350mg/m2 q3weeklyIrinotecan 350mg/m2 q3weekly

10 Endpoint= PFS


Toxicity

Grade 3/4 Toxicity Cetuximab + Irinotecan

N = 638, %

Irinotecan

N = 629, %

Any AE > 5% 71.6 56.8

Diarrhea 28.8 16.2

Vomiting 6.1 6.4

Fatigue 9.2 4.9

Acne-like Rash 8.2 0.5

Infusion Reaction 1.4 0.8

Hypomagnesemia

3.3 0.4


Efficacy

Cetuximab + Irinotecan

N=648

Irinotecan

N=650

P-value

Overall Response 16.4% 4.2% 0.0001

CR 1.4% 0.2%

PR 15.0% 4.0%

Disease Control

(CR+PR+SD)

61.4% 45.8% 0.0001

Median PFS 4.0 months 2.6 months 0.0001

Median OS 10.7 months 9.9 months 0.7115

HR = 0.69 (0.62-0.78)

HR = 0.98 (0.85-1.11)


Post-Study Therapy

Post-Study Therapy

Cetuximab + Irinotecan(N = 648)

Irinotecan (N = 650)

Any 3rd Line Rx

57% 65%

Cetuximab 11% 47%

Bevacizumab 16% 14%


Survival by Skin Reaction: Cetuximab + Irinotecan

Skin Reaction Median OS

None 5.8 months

Grade 1/2 11.7 months

Grade 3/4 15.6 months


MRC: EXPLORE

RANDOMI ZE

1:11:1

Cetuximab + FOLFOXN=52

FOLFOXN=50

Prior IrinotecanChemotherapyEGFR+ (IHC)

Metastatic CRCN=102

Polikoff Proc ASCO 2005


10 Endpoint= OS


EXPLORE

• Planned sample size N=1100

• Trial stopped early December 2004 because of poor accrual– Widespread adoption of FOLFOX in first-line

setting


Efficacy

Cetuximab + FOLFOX

N=43

FOLFOX

N=42

Response Rate 20.9% 9.5%

Stable Disease Rate

46.5% 61.9%

Median PFS 4.4 months 4.1 monthsp=0.48


Second-line Therapy:Panitumumab + Chemotherapy


Panitumumab, Irinotecan & Cyclosporin in COLOrectal

Cancer Therapy (PICCOLO): Ongoing

RANDOMI ZE

1:1:11:1:1

Irinotecan + Panitumumab

Irinotecan + Cyclosporin

N=1269 (Target)Prior 5-FU +/- Oxali +/- Bev

No EGFR testing

10 Endpoint= PFS

Irinotecan alone


Second-line Therapy:Cetuximab + Chemotherapy +

anti-VEGF


SWOG S0600/ECOG/NCCTG/NCIC: Ongoing

RANDOMI ZE

1:1:11:1:1

Irinotecan/FOLFIRI + Cetuximab + Bevacizumab

Irinotecan/FOLFIRI + Cetuximab

N=1250 (Target)Prior Oxali-based CT

Prior Bev allowedNo EGFR testing

No Prior anti-EGFR therapy

10 Endpoint= OS

Irinotecan/FOLFIRI + Bevacizumab


Summary - Second Line• EPIC trial shows that addition of Cetuximab to FOLFIRI

produces statistically significant improvement in response rate and PFS

• PFS improvement of questionable clinical significance with no overall survival benefit and added toxicity – lack of OS benefit due to cross over to cetuximab setting on

progression in standard arm• S0600 will address whether addition of Cetuximab + anti-

VEGF therapy to Irinotecan-based treatment can improve OS after progression on oxaliplatin-based chemotherapy

• At present, data do not support routine use of anti-EGFR mAb therapy in 2nd line setting


Third-line Therapy:Cetuximab Monotherapy


EGFR EGFR testing testing

by IHCby IHC

* Cetuximab 400 mg/m* Cetuximab 400 mg/m2 2 IV week 1 then IV week 1 then 250 mg/m250 mg/m22 IV weekly IV weekly

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

REGISTER

RANDOMI ZE

1:11:1

Cetuximab* + BSC

Best Supportive Care alone

NCIC CO.17

Jonker DJ NEJM 2007

N=572Prior 5FU, Iri, and Oxali-CT

EGFR expression required

10 Endpoint= OS


Patient Characteristics

Cetuximab + BSC

N = 287 (%)

BSC

N = 285 (%)

GENDER Male/ Female 64.8/35.2 63.9/36.1

AGE (years) Median [range]

63 [28.6 - 88.1] 64 [28.7 - 85.9]

> 65 years 38.3 44.6

ECOG Performance

Status

0 25.1 22.5

1 51.6 54.0

2 23.3 23.5

Type of Prior Treatment

TS Inhibitor 100.0 100.0

Irinotecan 96.5 95.8

Oxaliplatin 97.9 97.5


Toxicity: Key Differences

Grade 3/4 toxicityCetuximab +

BSC

N = 287 (%)

BSC

N = 285 (%)

Rash 11.8 0.4

Non-neutropenic Infection

12.8 5.5

Hypomagnesemia 5.8 0

Pain (other than abdominal)

14.9 7.3


Efficacy


BSC

N = 287 (%)

BSC

N = 285 (%)

Partial Response 8.0 0

Stable Disease 31.4 10.9

Median PFS 1.9 months 1.8 months

Median OS 6.1 months 4.6 months

HR = 0.71 (0.59-0.85)

HR = 0.79 (0.65-0.95)


Survival by Skin Reaction: Cetuximab Monotherapy

Skin Reaction Median OS

None 2.6 months

Grade 1 4.8 months

Grade 2 or higher

8.4 months


Quality of Life

• Improved at 8 & 16 weeks in physical functioning and global QoL in Cetuximab + BSC arm vs. BSC alone

Au H Proc ASCO 2007


Panitumumab 3rd Line Monotherapy Trial

EGFR EGFR testing testing

by IHCby IHC

REGISTER

RANDOMI ZE

1:11:1

Panitumumab + BSCN=231

BSC aloneN=232

10 Endpoint= PFS

Panitumumab + BSCN=176

* Panitumumab 6 mg/m* Panitumumab 6 mg/m2 2 IV Q2weekly IV Q2weekly

N=463Prior 5FU, Iri, and Oxali-CT

EGFR expression required

Optional Cross-Over on Progression

Van Cutsem E JCO 2007


Patient Characteristics

Panitumumab + BSC

N = 231 (%)

BSC

N = 232 (%)

GENDER Male/ Female 63/37 64/36

AGE (years) Median [range]

62 [27 - 82] 64 [27 - 83]

ECOG Performance

Status

0 46 40

1 41 45

2

3

13

0

14

1

Prior lines of Chemotherapy

2 lines 100 100

3 lines 36 38


Toxicity

Grade 3/4 toxicityPanitumumab +

BSC

N = 231 (%)

BSC

N = 232 (%)

Acne-like Rash 7 0

Abdominal Pain 7 4

Erythema 5 2

General Physical Deterioration

7 2


Efficacy

Grade 3/4 toxicityPanitumumab +

BSC

N = 231 (%)

BSC

N = 232 (%)

Partial Response 10 0

Stable Disease 27 10

Median PFS 2.0 months 1.8 months

Median OS NR NR

HR = 0. 54 (0.44-0.66); p<0.0001

HR = 1.00 (0.82-1.22)


Survival by Skin Reaction: Panitumumab Monotherapy

Worst Skin Reaction

Median OS

Grade 1 5.9 months

Grade 2 or higher

7.9 months

Humblet Y Proc ASCO 2007

HR = 0.68; p=0.03


Quality of Life

• Trend towards improvement for Colorectal Cancer Related symptoms and overall health-related QoL in Panitumumab group

• Patients who developed skin rash on Panitumumab were bothered by their symptoms

Humblet Y Proc ASCO 2007


Third-line Therapy:Cetuximab + Chemotherapy


Bowel Oncology with Cetuximab Antibody (BOND-1)

RANDOMI ZE

2:12:1

Cetuximab aloneN=111

N=329Prior Iri-CT within

3 monthsEGFR+ (IHC)


10 Endpoint= Response


N=56


N=218

Cunningham DR NEJM 2004


Prior Therapy


N = 218 (%)

Cetuximab alone

N = 111 (%)

Lines of Prior Therapy

1st line 18.8 24.3

2nd line 36.2 36.9

≥3rd line 45.0 38.7

Prior Oxaliplatin 61.9 64.0


Toxicity


Irinotecan

N = 218 (%)

Cetuximab alone

N = 111 (%)

Diarrhea 21.2 1.7

Acne-like Rash 9.4 5.2

Neutropenia 9.4 0

Hypersensitivity Reaction

0 3.5


Efficacy


N = 218 (%)

Cetuximab alone

N = 111 (%)

Response 22.7 10.8

Disease Control 55.1 32.4

Time to Progression 4.1 months 1.9 months

Median OS 8.6 months 6.9 monthsHR = 0.54 (0.42-0.71)

HR = 0.91 (0.69-1.21)


Response Rate by EGFR staining

EGFR staining intensity

Cetuximab+

Irinotecan

Cetuximab

alone

Faint 20.8% 4.8%

Weak or Moderate

24.7% 12.8%

Strong 22.7% 11.7%

p=0.64


Response Rate by Skin Reaction

Skin Reaction

Cetuximab+

Irinotecan

Cetuximab

alone

None 6.3% 0

Grade 1 or 2 20.4% 11.6%

Grade 3 or 4 55.3% 33.3%

p<0.0001


BOND-2: Phase II

RANDOMI ZE

1:11:1

Cetuximab + Bevacizumab

N=41

N=81Prior Iri-CT within

3 monthsEGFR expression

not required

Cetuximab 400mg/m2 week 1; then 250mg/m2 weekly

Bevacizumab 5mg/kg every Q2weekly

Cetuximab + Bevacizumab +

IrinotecanN=40

Saltz L Proc ASCO 2005


Prior Therapy


Irinotecan

N = 40


N = 41

Median # Lines of Prior Therapy

3 3

Prior Oxaliplatin 85% 90%


Toxicity

Grade 3/4 toxicity


Irinotecan

N = 40 (%)


N = 41(%)

Diarrhea 24 0

Acne-like Rash 17 20

Neutropenia 22 0

Fatigue 10 0


Efficacy


Irinotecan

N = 40 (%)


N = 41 (%)

Partial Response 37% 20%

Disease Control NR NR

Median Time to Progression

7.9 months 5.6 months

Median OS NR NR


Third-line Therapy:Cetuximab + Chemotherapy +

anti-VEGF


BOND-3: Phase II (Ongoing)

RANDOMI ZE

1:11:1


Prior Bevacizumab + Chemotherapy

Cetuximab 400mg/m2 week 1; then 250mg/m2 weekly

Bevacizumab 5mg/kg every Q2weekly


Irinotecan


Summary – Third line

• Cetuximab monotherapy after progression on oxaliplatin and irinotecan based chemotherapy is the only setting in which EGFR monoclonal antibody therapy has shown a survival benefit in colorectal cancer– Survival benefit modest but cetuximab monotherapy

also associated with significant improvement in quality of life

• Panitumumab alone and Cetuximab + Irinotecan both demonstrate a significant improvement in PFS in the third-line setting


Summary – Third line

• Should Cetuximab be given with Irinotecan in 3rd line?– Cetuximab + Irinotecan combination demonstrates

best response rates and TTP benefits (cross trial comparisons) but unable to determine impact of irinotecan on QOL


# pts RR % Median PFS/TTP

Median OS QoL

FIRST

LINE

PACCE

(Oxali only)

793 39 vs 41 9.0 vs 10.5 18.6 vs NR ?

CRYSTAL 1198 47 vs 39 8.9 vs 8.0 ? ?

SWOG 80203

238 52 vs 38 8.5 vs 9.4 ? vs 16.9 ?

OPUS 338 46 vs 37 ? ? ?

SECOND LINE

EPIC 1298 16 vs 4 4.0 vs 2.6 10.7 vs 9.9 Improved

EXPLORE 102 21 vs 10 4.4 vs 4.1 ? ?

THIRD

LINE

BOND-1 329 23 vs 11 4.1 vs 1.9 8.6 vs 6.9 ?

P-mab

3rd line

463 10 vs 0 2.0 vs 1.8 NS ?Improved

NCIC CO.17 572 8 vs 0 1.9 vs 1.8 6.1 vs 4.6 Improved

statistically significant results in RED


The Bottom Line forCanadian Medical Oncologists


• EGFR monoclonal antibody therapy is active in metastatic disease with relatively mild toxicity as monotherapy

• Clinical trial data most strongly support use of EGFR monoclonal antibody therapy in the third-line setting, after progression on Oxaliplatin and Irinotecan based therapy– According to BOND-1 data, combination of Cetuximab +

Irinotecan in 3rd line more active than Cetuximab alone

Efficacy and Toxicity


• Cetuximab and Panitumumab appear to have similar efficacy and toxicity in the third line setting as monotherapy

• Access to Cetuximab and Panitumumab is difficult in Canada– Only cetuximab is approved by Health Canada and it

is not being marketed (or funded)

Efficacy and Toxicity


• Results of PACCE suggest that the combination of Panitumumab, Bevacizumab, and chemotherapy is toxic with less efficacy in the first line setting

• Excess toxicity of anti-EGFR therapy with anti-VEGF agent and chemotherapy not seen with Cetuximab in BOND 2 or CAIRO-2– Suggests that Cetuximab may be more easily combined with

anti-VEGF and chemotherapy than Panitumumab– Results of SWOG 80405 and CAIRO-2 trial will provide further

insight

Anti-EGFR and Anti-VEGF Combinations


• Future biomarker studies will attempt to address which subgroups of patients will derive benefit from EGFR blockade

• To date, studies suggests that level of EGFR expression via IHC is NOT a useful predictor of response

• CRYSTAL, BOND-1, NCIC CO.17, and Panitumumab 3rd line monotherapy trial demonstrate that skin rash may be an early surrogate marker for favourable clinical outcome– However, it is not clear from the current data if skin rash on

EGFR monoclonal antibody therapy is an early surrogate marker for BENEFIT from EGFR blockade or simply an early surrogate marker of a favourable prognosis

– Early data from EVEREST raises the intriguing possibility that “early skin rash non-responders” may benefit from dose-escalation of Cetuximab needs further testing

Patient Selection for anti-EGFR Therapy


• Preliminary data from Panitumumab 3rd line monotherapy trial suggests that patients with K-RAS mutation do not benefit from EGFR blockade (Amado ECCO 2007)– Similar to data from EGFR therapy in non-

small cell lung cancer and pancreatic cancer– Analyses of K-RAS status from other EGFR

monoclonal antibody trials are in progress

Patient Selection for anti-EGFR Therapy


Acknowledgements

We would like to thank Dr. Mark Rother for his helpful contributions to this educational program

Www.OncologyEducation.ca Defining the Role of EGFR Monoclonal Antibody Therapy in Metastatic...

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