ix plus BSC and 21.0% on BSC alone, a difference of 38.7% [95% CI: 27.4, 50.0]. The difference in median PFS in the mutant KRAS group was 0 weeks. The progression-free survival rates at the first scheduled visit (week 8) in the mutant KRAS group were 21.4% on Vectibix plus BSC and 28.0% on BSC alone, a difference of -6.6% [95% CI: -19.0, 5.9]. There were no differences in overall survival seen in either group. In the wild-type KRAS group the response rate was 17% for panitumumab and 0% for BSC. In the mutant KRAS group there were no responses in either treatment arm. Stable disease rates in the wild-type KRAS group were 34% for panitumumab and 12% for BSC. The stable disease rates in the mutant KRAS group were 12% for panitumumab and 8% for BSC. Response rate (investigator assessment) in patients that crossed over to panitumumab after progression on BSC alone was 22% (95% CI: 14.0, 31.9) for those with wild-type KRAS tumours and 0% (95% CI: 0.0, 4.3) for those with mutant KRAS tumours.
PFS – Patients with mutant and wild-type KRAS
Wild-Type KRAS
Unscheduled tumour assessments were moved to the nearest scheduled timepoint
Mutant KRAS
Unscheduled tumour assessments were moved to the nearest scheduled timepoint
Clinical efficacy in combination with chemotherapy
Summary of key final efficacy results in pivotal studies: Vectibix in combination with chemotherapy.
First-line mCRC
FOLFOX± Vectibix
wild-type KRAS
Second-line mCRC
FOLFIRI± Vectibix
wild-type KRAS
Pmab
(n = 325)
Control
(n = 331)
Pmab
(n = 303 )
Control
(n = 294 )
KRAS Ascertainment
93%
91%
Response Rate
57%
48%
36%
10 %
PFS Hazard Ratio
(95% CI)
0.799
(0.674, 0.946) P = 0.0092
0.820
(0.692, 0.972) P = 0.0231
Median PFS (months)
(95% CI)
10.0
(9.3, 11.4)
8.6
(7.5, 9.5)
6.7
(5.8, 7.4)
4.9
(3.8, 5.5)
Absolute benefit (months)
1.4
1.8
OS Hazard Ratio
(95% CI)
0.878
(0.728, 1.058) P = 0.1710
0.922
(0.775, 1.098) P = 0.3660
Median OS (months)
(95% CI)
23.9
(20.3, 27.7)
19.7
(17.6, 22.7)
14.5
(13.0, 16.1)
12.5
(11.2, 14.2)
Absolute benefit (months)
4.2
2.0
First-line combination with FOLFOX
The efficacy of Vectibix in combination with oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (FOLFOX) was eva luated in a randomised, controlled trial of 1183 patients with mCRC with the primary endpoint of progression-free survival (PFS). Other key endpoints included the overall survival (OS), objective response rate (ORR), time to response, time to progression (TTP), and duration of response. The study was prospectively analysed by tumour KRAS status which was eva luable in 93% of the patients A summary of results in patients with wild-type KRAS mCRC are presented in the table above.
In an exploratory covariate analysis of patients with an ECOG 2 performance status (n = 40), shorter median PFS was observed in the panitumumab plus FOLFOX arm (4.8 months) than in the FOLFOX alone arm (7.5 months), (hazard ratio, 1.800, 95% CI: 0.879, 3.686; p = 0.1060). In patients with an ECOG performance status of 0 or 1 (n = 616), the median PFS was 10.8 months in the panitumumab plus FOLFOX arm and 8.7 months in the FOLFOX alone arm (hazard ratio 0.76 |
