Beruflich Dokumente
Kultur Dokumente
PFS OS RR
Therapy N
(months) (months) (%)
Approx. 56 days
after end of treatment
• Objectives
– To estimate the effect of KRAS mutation status on
objective response rate and other measures of efficacy
for 1st-line treatment of mCRC patients with
panitumumab plus FOLFIRI
– To describe the safety profile of this combination
therapy in the 1st-line setting
*Two patients did not have measurable disease per RECIST guidelines at baseline and were therefore not included in the
analysis of response rate. N/A = not applicable; Disease control rate = CR + PR + SD
20
Resection rate (%)
10
15
7
0
KRAS WT KRAS MT
(N=85) (N=58)
• Resection rates were 15% (95%CI: 8.3% to 24.5%) and 7% (95% CI: 1.9% to
16.5%) in the KRAS WT and MT groups, respectively
Events Median
100 N (%) (95% CI) months
KRAS WT (N=86) 44 (51) 8.9 (7.6 - 14.3)
90
Proportion Event-Free (%)
1Centre
René Gauducheau, Nantes, France; 2Ospedale Niguarda Ca’ Granda, Milan, Italy;
3The Beatson West Of Scotland Cancer Centre, Glasgow, United Kingdom; 4Vall d'Hebron
University Hospital, Barcelona, Spain; 5Mount Sinai Hospital, Toronto, Canada; 6Hospital de
Gastroenterología, Buenos Aires, Argentina; 7Centre du Cancer de l'Université Catholique de
Louvain, Brussels, Belgium; 8The Royal Marsden NHS Foundation Trust, London, United
Kingdom; 9Amgen Inc., Thousand Oaks, California
KRAS SEQUENCE
ANALYSIS
(Selected Samples from
Study
CRC Phase 2 Studies) Unblinding
and Primary
20020408 Analysis
KRAS 31 July 2009
ANALYSIS
• Primary endpoint:
– PFS (by blinded central radiology review)
OS, MT KRAS
α=0.05
KRAS WT KRAS MT
PANITUMUMAB PANITUMUMAB KRAS WT KRAS MT
+ FOLFOX4 + FOLFOX4 FOLFOX4 FOLFOX4
(N=325) (N=221) (N=331) (N=219)
WT KRAS – % 60 60 60
MT KRAS – % 40 40 40
KRAS tumour status was determined using the DxS kit (Manchester, UK)
that tests the 7 most common KRAS mutations in codons 12 and 13.
80%
70%
HR=0.80 (95% CI: 0.66 - 0.97)
60% p=0.02
50%
40%
30%
20%
10%
0%
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Months
Patients at risk:
Panitumumab+FOLFOX4 325 313 294 284 254 243 204 187 156 145 111 94 73 57 39 28 22 14 10 4 1 0 0 0
FOLFOX4 alone 331 321 296 281 242 231 185 172 127 113 82 65 41 36 29 22 16 12 10 2 1 1 1 0
p=0.07
60%
50%
40%
30%
20%
10%
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months
Patients at risk:
Panitumumab
+FOLFOX4 325 315 310 288 266 242 227 217 207 189 164 135 104 74 55 29 9 2 0
FOLFOX4 alone 331 320 301 281 265 242 223 207 188 170 145 116 77 56 36 21 9 3 0
Partial response 55 47
Stable disease 30 36
Progressive disease 7 11
*P = 0.068 (descriptive)
100% 100%
KRAS WT KRAS MT
90% 90%
80% 80%
Proportion Event-Free
Proportion Event-Free
70% 70%
60% 60%
50% 50%
40% 40%
30% 30%
20% 20%
10% 10%
0% 0%
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Months Months
HR=0.80 (95% CI: 0.66 - 0.97) HR=1.29 (95% CI: 1.04 - 1.62)
p=0.02 p=0.02
90%
KRAS WT 90%
KRAS MT
80%
Survival Probability
Survival Probability
80%
70% 70%
60% 60%
50% 50%
40% 40%
30% 30%
20% 20%
10% 10%
0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months Months
HR=0.83 (95% CI: 0.67 - 1.02) HR=1.24 (95% CI: 0.98 - 1.57)
p=0.07 p=0.07
Median actual follow-up time (data cut-off 28 August 2009): 20 months pmab + FOLFOX4 and 17 months FOLFOX4
(KRAS wt), 14 months pmab + FOLFOX4 and 16 months FOLFOX4 (KRAS MT)
A pre-specified descriptive final analysis of OS is planned after a 2.5 year minimum follow-up period
Central Review
Panitumumab
+ FOLFOX4 FOLFOX4
(N=215) (N=211)
Objective tumor response, % 40 40
(95% CI)* (33 - 46) (34 - 47)
Complete response 0 0
Partial response 40 40
Stable disease 38 43
Progressive disease 13 11
Siena S, et al. ASCO-GI 2010, #283, oral presentation; Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
Overall conclusions
• In 1st-line treatment of mCRC, KRAS status was
predictive of efficacy of panitumumab in combination
with
– FOLFOX4 (PRIME) or
– FOLFIRI (phase 2 studies)