1. This study was funded by Amgen Inc.
Interim results from PACCE: irinotecan (Iri)/bevacizumab (bev) ± panitumumab (pmab) as first-line treatment (tx) for metastatic colorectal cancer (mCRC)
J. Randolph Hecht,1 Edith Mitchell,2 Tarek Chidiac,3 Carroll Scroggin,4 Christopher Hagenstad,5 David Spigel,6 John Marshall,7 Allen Cohn,8 Sam Suzuki,9 Thomas Griffin9
1UCLA School of Medicine, Los Angeles, CA; 2Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA; 3Mid Ohio Oncology/Hematology, Inc, Columbus, OH; 4NEA clinic, Jonesboro, AR; 5Suburban Hematology-Oncology Associates, Lawrenceville, GA; 6Sarah Cannon Research Institute, Nashville, TN; 7Georgetown University Hospital, Washington, DC; 8Rocky Mountain Cancer Centers, Denver, CO; 9Amgen Inc., Thousand Oaks, CA
This study was funded by Amgen Inc.

2. Introduction
Panitumumab is a fully human monoclonal antibody that targets the epidermal growth factor receptor (EGFr) and is approved as monotherapy in the US for the treatment of refractory mCRC
Early studies have suggested that combining EGFr, VEGF inhibitors, and chemotherapy may improve efficacy1,2
PACCE was a US, community-based study designed to compare the efficacy and safety of bevacizumab and chemotherapy +/- panitumumab as first-line treatment for mCRC
This is an interim analysis for data available as of May 31, describing the safety and efficacy for the Iri-CT based cohort from PACCE (trial discontinued only panitumumab therapy in March after a planned interim analysis of ~231 PFS events in the Ox-CT cohort)
1Shaheen et al. Brit J Cancer 2001;85:
2Saltz LB et al. ASCO Abstract #3508 (BOND2)

3. PACCE: Panitumumab Advanced Colorectal Cancer Evaluation
Study Schema
PACCE: Panitumumab Advanced Colorectal Cancer Evaluation
Randomized, Open-Label, Controlled Phase 3b Trial
Panitumumab 6 mg/kg Q2W
+ Ox-CT
Bevacizumab
Ox-based CT
(eg, FOLFOX)
N = 800
Inv choice S C R E N I G R A N D O M I Z E
1:1
Ox-CT
+ Bevacizumab
Panitumumab 6 mg/kg Q2W
+ Iri-CT
+ Bevacizumab
Iri-basedCT
(eg, FOLFIRI)
N = 200
Inv choice
1:1
Iri-CT
+ Bevacizumab
Stratification Factors: ECOG score, prior adjuvant tx, disease site, Ox doses/Iri regimen, number of metastatic organs
Tumor assessments: Q12W until disease progression or intolerability

4. Investigator Choice – Iri-CT Regimens
Irinotecan
Leucovorin (LV)
5-Fluorouracil (5-FU)
FOLFIRI
180 mg/m2 IV over 90 min on Day1 per cycle
200 mg/m2 IV over 2 hrs on Day1
400 mg/m2 IV bolus over 2-4 min, followed 2400mg/m2 continuous IV over 46 hrs for the first 2 cycles, increased to 3000 mg/m2 if no toxicity >grade 1
Douillard
180 mg/m2 IV over 2 hrs on Day1 per cycle
200 mg/m2 IV over 2 hrs on Day1 and 2
400 mg/m2 IV bolus over 2-4 min, followed by 600 mg/m2 continuous IV over 22 hrs Day 1 and Day 2
Other Iri-CT Q2W
TBD by physician

5. Key Eligibility Criteria
Age ³ 18 years old
Measurable mCRC per modified RECIST criteria
ECOG status 0 or 1
Adequate hematologic, renal, and hepatic function
No prior chemotherapy or biologic therapy for mCRC
No adjuvant chemotherapy within 6 months
No major surgery within 28 days of randomization or elective and/or planned major surgical procedures during the trial
No clinically significant cardiovascular disease within 1 year prior to randomization
No EGFr testing required

6. Study Endpoints and Design Characteristics
Primary endpoint of the PACCE study:*
Progression-free survival (PFS) by central review in the Ox-CT cohort
To detect a 30% improvement in median PFS in the panitumumab plus bev/Ox-CT vs the bev/Ox-CT
Planned interim analysis at ~231 Ox-CT PFS events
Iri-CT cohort analyses were descriptive only
Safety
Efficacy including:
Overall response rate (central and local review)
PFS (central and local review), TTF, OS
Exploratory biomarker analyses (eg, KRAS)
*Powered for oxaliplatin cohort only; descriptive for irinotecan cohort

7. Treatment: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
pmab+ bev/Iri-CT (N=115)
bev/Iri-CT (N=115)
Patients randomized, n (%)
115 (100)
Patients received any first-line treatment, n (%)
112 (97)
Median follow-up, weeks
Range
37.6
Chemotherapy regimen received on week 1, n (%)a
FOLFIRI
97 (87)
104 (93)
Douillard
9 ( 8)
3 ( 3)
Other Iri-CT
6 ( 5)
5 ( 4)
aOf those who received any first-line treatment

8. Baseline Demographics and Characteristics: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
pmab+ bev/Iri-CT (N=115)
bev/Iri-CT (N=115)
Male, % 49 62
Race, %
White
Black
Hispanic Other 75 16
5 4 74 14
12 0
Median age (range), years
60.0 (35 – 84)
59.0 (23 – 80)
Age  65, % 38 28
Baseline ECOG, %
0 1 59 41 64 36
Prior Adjuvant Therapy, % 33 31
Metastatic organs, % 1
>1 40 60 46 54

9. Summary of Adverse Events: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
pmab+ bev/Iri-CT (N=111)
bev/Iri-CT (N=113)
Any event, % 99
100
Grade 3 56 43
Grade 4 23 15
Grade 5* 5 1
Pmab-related grade 5 2
n/a
Any serious (SAE), % 54 33
Ended all first-line treatment due to AE, % 17
Ended panitumumab treatment due to AE, %
Panitumumab treatment-related SAE, % 16
AEs as reported by investigator
Safety set included all patients who were dosed. Graded per NCI CTCAE v3.0
*As reported by investigator – does not include disease progression (ie, neoplasms); n/a= not applicable

10. Grade 3 or 4 Adverse Events of Interest: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
pmab+bev/Iri-CT
(N=111)
bev/Iri-CT
(N=113)
Grade 3 n (%)
Grade 4 n (%)
Skin toxicitya
41 ( 37)
0 (0)
Diarrhea
30 (27)
1 (1)
10 (9)
Neutropenia
16 (14)
3 (3)
19 (17)
5 (4)
Dehydration
15 (14)
7 (6)
Infectionsb
13 (12)
2 (2)
Nausea
11 (10)
Hypokalemia
Vomiting
9 (8)
8 (7)
Paronychia
4 (4)
Hypomagnesemia
Hypertension
Deep venous thrombosis
14 (13)
Pulmonary embolismc
12 (11)
6 (5)
MedDRA v 9.0 preferred terms; graded per NCI CTCAE v 3.0
aSkin toxicity included multiple terms from the skin and subcutaneous and infections system organ class (SOC)
bGrade 5 infections occurred in 2 (2%) pmab + bev/Iri-CT pts
cGrade 5 pulmonary embolism occurred in 1 (1%) pmab + bev/Iri-CT pts
Grade 5 gastrointestinal perforations occurred in 2 (2%) pmab + bev/Iri-CT pts

11. Overall Response Rate: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
Central Reviewa
Local Reviewa
pmab+ bev/Iri-CT (N=115)
bev/Iri-CT (N=115)
Best ORR
43%
39%
55%
46%
Complete response 0%
10% 6%
Partial response
44%
40%
Stable disease
27%
38%
23%
30%
Progressive diseaseb
13% 3% 5%
Not done/Unevaluablec
17%
19%
15%
aCT scans performed Q12W; responses did not require confirmation bCentral review unable to evaluate clinical disease progression (ie, non-radiographic PD); central review unable to accurately evaluate PD after surgical resections cIncluded missing and unreadable scans

12. Interim PFS – Iri-CT Cohort (May 2007 Data Cutoff)
Central Reviewa
Local Reviewb
# PFS events (%)
Median (95%CI), mos
54 (47)
10.1 (8.2, 13.7)
43 (37)
11.7 (9.0, 13.2)
# PFS events (%)
Median (95%CI), mos
62 (54)
11.0 (9.1, 13.6)
53 (46)
10.7 (9.0, 12.5)
Pmab+bev/Iri-CT
Bev/Iri-CT
HR= 1.21 (95% CI: 0.80, 1.82)*
HR= (95% CI: 0. (0.63, 1.34)*
*Descriptive only
*Descriptive only 0%
20%
40%
60%
80%
100% 5 10 15 20 25 0%
20%
40%
60%
80%
100% 5 10 15 20 25
Months
Central vs local review background:
Original primary endpoint was PFS by local review; Protocol amended in May 2006 to primary endpoint by central review
Central review in PACCE protocol is not a typical phase 3 mCRC central review process:
- single radiologist read, no oncologist review
- clinical (non-radiographic) disease progression unable to be evaluated by central review
CT scans were performed every 12-weeks in PACCE (typically Ph3 mCRC studies are every 8 weeks)
2) Differences in censoring rules for central and local
- Central censoring: if endpoint not reached and there were no further scans, pt was censored back to their last scan date (Q12W)
- Local censoring: if endpoint not reached and there were no further scans, pt was censored back to their last investigator contact (Q2W)
Bev/Iri-CT cohort had more censoring than pmab+bev/Iri-CT cohort in both central and local reviews
Central review unable to assess disease progression after surgical resections
Per the PACCE protocol, central review is unable to accurately evaluate patients’ disease progression after surgery
Potential investigator bias for local review
Months
Pmab
115 74 23 7 1
115 86 33 7 2
Censored 19 32 6 4 9 31 11 1 1
No Pmab
115 76 23 6 1
115 85 27 6
Censored 29 34 7 2 14 34 11 3
aCensoring based on last available scan read centrally Q12W
bCensoring based on last day of patient contact or visit Q2W
Central vs Local Review
Differences in censoring rules; more early censoring in central review and in bev/Iri-CT cohort
Central review unable to assess clinical disease progression
Central review unable to accurately evaluate PD after surgical resections
Investigator bias

13. PFS - Differences Between Central vs Local Review
Differences in censoring rules
Central censoring: if endpoint not reached, pt was censored back to their last scan date (Q12W)
Local censoring: if endpoint not reached, pt was censored back to their last investigator contact (Q2W on treatment, Q12W post-treatment follow-up)
More early censoring in central review and in bev/Iri-CT cohort
Central review unable to assess clinical disease progression
Per protocol, central review defined as single radiologist read, no oncologist review
Central review unable to accurately evaluate PD after surgical resections
Potential investigator bias for local review
Central vs local review background:
Original primary endpoint was PFS by local review; Protocol amended in May 2006 to primary endpoint by central review
Central review in PACCE protocol is not a typical phase 3 mCRC central review process:
- single radiologist read, no oncologist review
- clinical (non-radiographic) disease progression unable to be evaluated by central review
CT scans were performed every 12-weeks in PACCE (typically Ph3 mCRC studies are every 8 weeks)
2) Differences in censoring rules for central and local
- Central censoring: if endpoint not reached and there were no further scans, pt was censored back to their last scan date (Q12W)
- Local censoring: if endpoint not reached and there were no further scans, pt was censored back to their last investigator contact (Q2W)
Bev/Iri-CT cohort had more censoring than pmab+bev/Iri-CT cohort in both central and local reviews
Central review unable to assess disease progression after surgical resections
Per the PACCE protocol, central review is unable to accurately evaluate patients’ disease progression after surgery
Potential investigator bias for local review

14. Other Efficacy Endpoints: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
pmab+ bev/Iri-CT (N=115)
bev/Iri-CT (N=115)
Time to Treatment Failure, Median (95% CI), months
6.6 ( )
6.0 ( )
Overall Survival,
Median (95% CI), months
20.7 ( NE)
20.5 ( NE)
Deaths events, n (%)a
26 (23)
18 (16)
Within 60 days of first dose, n (%)
5 ( 4)
2 ( 2)
Within 30 days of last dose of 1st line tx, n (%)
8 ( 7)
3 ( 3)
aDeaths at any time including long-term follow-up (post-study treatment)
NE= not evaluable

15. Reasons for First-Line Treatment Discontinuation: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
pmab + bev/Iri-CT (N=115)
bev/Iri-CT
(N=115)
Patients discontinued first-line tx, n (%)
102 (89)
99 (86)
Progressive events, n (%)a
42 (41)
29 (29)
Disease progression
36 (35)
27 (27)
Deaths
6 (6)
2 (2)
Non-progressive events, n (%)a
60 (59)
70 (71)
Adverse events
17 (17)
Protocol violation
3 (3)
5 (5)
Consent withdrawn/ refused treatment
15 (15)
26 (26)
Otherb
25 (25)
33 (33)
aOf those who discontinued first-line treatment
bOther included end of first-line treatment without progression, requirement for alternative therapy, administrative, lost to follow-up, and other

16. Relative Dose Intensity
Treatment Exposure: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
Dose Delays % Pts
Dose Reductions % Pts
Relative Dose Intensity
(RDI) %
pmab+ bev/Iri n=111
bev/Iri n=113
pmab+ bev/Iri
n=111
bev/Iri
N=113
Panitumumab 65
n/a 34 83
Bevacizumab 61 45 1 3 88 92
Irinotecan 63 46 21 18 81
5-FU
61a
45a
24a
16a
81b
87b
% Pts
Inf 5-FU/ Iri/Bev ≥ 85% 44
aBolus 5-FU bInfusional 5-FU n/a=not applicable

17. Prevalence of Mutant KRAS: Iri-CT Cohort (Interim Analysis, May 2007 Data Cutoff)
pmab+ bev/Iri-CT
bev/Iri-CT
Patients randomized, n
115
KRAS not tested, n (%)
6 (5)
8 (7)
KRAS tests failed, n (%)
3 (3)
9 (8)
Did not receive treatment, n (%)
1 (1)
Patients included in KRAS analysis, n (%)
103 (90)
97 (84)
Patients included in KRAS analysis, n
103 97
Wild-type KRAS, n (%)
57 (55)
58 (60)
Mutant KRAS, n (%)
46 (45)
39 (40)

18. pmab+ bev/Iri-CT (n/N) %
Overall Response Rate By KRAS Status (Interim Analysis, May 2007 Data Cutoff)
Central Review N
pmab+ bev/Iri-CT (n/N) %
bev/Iri-CT (n/N) %
Odds Ratioa (95% CI)
Wild-type KRAS
115
31/57 (54)
27/58 (47)
1.42 ( )
Mutant KRAS 85
14/46 (30)
15/39 (38)
0.59 ( )
KRAS efficacy set
200
45/103 (44)
42/97 (43)
1.00 ( )
Iri-CT ITT set
230
49/115 (43)
45/115 (39)
1.15 ( )
Local Review
40/57 (70)
34/58 (59)
1.71 ( )
19/46 (41)
17/39 (44)
0.81 ( )
59/103 (57)
51/97 (53)
1.28 ( )
63/115 (55)
53/115 (46)
1.45 ( )
aOdds ratio for pmab:control (greater than 1.0 favors pmab+bev/Iri-CT). Descriptive only

19. SUMMARY
This is a descriptive interim analysis of bev/Iri-CT +/- panitumumab in the PACCE study
Response rates were higher in the panitumumab + bev/Iri-CT cohort; no significant differences in PFS and OS between cohorts were observed
Most patients withdrew due to non-progressive events (59% on panitumumab + bev/Iri-CT arm, 71% on bev/Iri-CT arm), similar to the Ox-CT cohort, limiting the utility of PFS as a valid endpoint in this study
Increased response rates with panitumumab + bev/Iri-CT were seen only in wild-type KRAS patients; these findings are consistent with previously reported data on KRAS analyses in the monotherapy setting1-3
Further data collection and analyses are ongoing
1Amado RG et al. JCO 2008, Manuscript in press
2Khambata-Ford S et al. JCO 2007; 25:
3Lievre A et al. Cancer Res 2006;66:

20. SUMMARY (cont.)
Phase 3 registrational studies are currently ongoing to investigate panitumumab with chemotherapy alone in first- line and second-line mCRC
Study investigates FOLFIRI +/- panitumumab in second-line mCRC (Peeters et al., Abstract #335, Poster #A56)
PRIME/Study investigates FOLFOX +/- panitumumab in first-line mCRC (Douillard et al., Abstract #443, Poster #A63)
Independent data monitoring committees for these studies have recommended continuation per protocol

21. ACKNOWLEDGEMENTS
Patients who participated in this study and their families
All investigators, co-investigators, and study staffs at 194 sites across the US
The Amgen study team