2; 95% CI: 0.640, 0.907; p = 0.0022).
In patients with wild-type KRAS mCRC (n = 656) the estimated median PFS was 10.0 months (95% CI: 9.3, 11.4) in the panitumumab plus FOLFOX arm and 8.6 months (95% CI: 7.5, 9.5) in the FOLFOX alone arm, an absolute difference of 1.4 months. PFS was significantly improved in the panitumumab plus FOLFOX arm compared to the FOLFOX alone arm (p-value = 0.0092). The estimated hazard ratio was 0.799 (95% CI: 0.674, 0.946) favouring the panitumumab plus FOLFOX arm. Based on primary analyses, the estimated PFS rate (95% CI) at twelve (12) months was 45% (39%, 51%) in the panitumumab plus FOLFOX arm and 33% (28%, 39%) in the FOLFOX alone arm.
The estimated median OS was 23.9 months (95% CI: 20.3, 27.7) in the panitumumab plus FOLFOX arm and 19.7 months (95% CI: 17.6, 22.7) in the FOLFOX alone arm, an absolute difference of 4.2 months. The difference did not achieve statistical significance (p = 0.1710). The hazard ratio was 0.878 (95% CI: 0.728, 1.058), favouring the panitumumab plus FOLFOX arm. Based on primary analyses, the estimated OS rate (95% CI) at twenty-four (24) months was 49% (43%, 55%) in the panitumumab plus FOLFOX arm and 40% (35%, 46%) in the FOLFOX alone arm.
Subsequent chemotherapy (irinotecan, oxaliplatin, or fluoropyrimidine) was given to 191 (59%) patients in the panitumumab plus FOLFOX arm and 214 (65%) patients in the FOLFOX alone arm. Subsequent anti-EGFR therapy was received by 42 (13%) patients in the panitumumab plus FOLFOX arm and 84 (25%) patients in the FOLFOX alone arm. The median time to subsequent chemotherapy was 11.5 months in the panitumumab plus FOLFOX arm and 10.0 months in the FOLFOX alone arm. The median time to anti-EGFR therapy was 21.5 months (panitumumab plus FOLFOX) and 15.6 months (FOLFOX alone). The role of subsequent anti-EGFR therapy or chemotherapy on the estimated OS treatment effect is unknown.
For objective tumour response, also a secondary endpoint, there were 181 (57%) (95% CI: 51%, 63%) responders in the panitumumab plus FOLFOX arm, and 154 (48%) (95% CI: 42%, 53%) responders in the FOLFOX alone arm. The odds ratio was 1.47 (95% CI: 1.07, 2.04) favouring the panitumumab plus FOLFOX arm. Stable disease was seen in 91 (29%) patients in the panitumumab plus FOLFOX arm and 117 (36%) patients in the FOLFOX alone arm.
The estimated mean (SD) for time to response for responding patients was 2.3 (0.9) months (panitumumab plus FOLFOX) versus 2.7 (1.3) months (FOLFOX alone). The duration of response was longer in the panitumumab plus FOLFOX arm (median 11.1 months [95% CI: 9.5, 13.0]) than in the FOLFOX alone arm (median 8.8 months [95% CI: 7.8, 9.7]). Time to disease progression was also longer in the panitumumab plus FOLFOX arm (median 10.8 months [95% CI 9.4, 12.4]) compared with the FOLFOX alone arm (median 9.2 months [95% CI 7.7, 9.9]; hazard ratio 0.774), favouring the panitumumab plus FOLFOX arm.
In an exploratory covariate analysis of patients with an ECOG 2 performance status (n = 40), shorter median OS was observed in the panitumumab plus FOLFOX arm (7.0 months) than in the FOLFOX alone arm (11.7 months) (hazard ratio 1.589; 95% CI: 0.800, 3.157; p = 0.1850). In patients with an ECOG performance status of 0 or 1 (n = 616), the median OS was 25.8 months in the panitumumab plus FOLFOX arm and 20.6 months in the FOLFOX alone arm (hazard ratio 0.837; 95% CI: 0.690, 1.017, p = 0.0735).
In a post-hoc analysis at the final data cutoff, the complete resection rate in subjects who had metastases to the liver only at baseline was 27.9% (95% CI: 17.2, 40. |
