8) in the panitumumab plus FOLFOX arm and 17.5% (95% CI: 8.8, 29.9) in the FOLFOX alone arm.
In patients with mutant KRAS mCRC (n = 440), PFS was inferior (p-value = 0.0194) in patients receiving Vectibix in combination with FOLFOX (7.4 months; 95% CI: 6.9, 8.1) than those patients receiving FOLFOX alone (9.2 months; 95% CI: 8.1, 9.9). The estimated median OS was shorter (p=0.14) in patients receiving Vectibix in combination with FOLFOX (15.5 months; 95% CI: 13.1, 17.6) compared with those receiving FOLFOX alone (19.2 months; 95% CI: 16.5, 21.7) (see sections 4.4 and 4.5). Vectibix is indicated only for the treatment of wild-type KRAS mCRC.
Second-line combination with FOLFIRI:
The efficacy of Vectibix in combination with irinotecan, 5-fluorouracil (5-FU) and leucovorin (FOLFIRI) was eva luated in a randomised, controlled trial of 1186 patients with mCRC with the primary endpoints of overall survival (OS) and progression-free survival (PFS). Other key endpoints included the 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 91% of the patients. A summary of results in patients with wild-type KRAS mCRC are presented in the table above.
In patients with wild-type KRAS mCRC (n = 597) a statistically significant difference in PFS in favour of panitumumab was demonstrated (p = 0.0231). The estimated median PFS times were 6.7 months (95% CI: 5.8, 7.4) in the panitumumab plus FOLFIRI arm and 4.9 months (95% CI: 3.8, 5.5) in the FOLFIRI alone arm, an absolute difference of 1.8 months. The hazard ratio was 0.820 (95% CI: 0.692, 0.972), favouring the panitumumab plus FOLFIRI arm. Based on primary analyses, estimated PFS rate (95% CI) at six (6) months was 56% (49%, 62%) in the panitumumab plus FOLFIRI arm and 41% (34%, 47%) in the FOLFIRI alone arm.
The estimated median OS was 14.5 months (95% CI: 13.0, 16.1) in the panitumumab plus FOLFIRI arm and 12.5 months (95% CI: 11.2, 14.2) in the FOLFIRI alone arm, an absolute difference of 2.0 months. The OS difference did not achieve statistical significance (p = 0.3660). The hazard ratio was 0.922 (95% CI: 0.775, 1.098), favouring the panitumumab plus FOLFIRI arm. Based on primary analyses, estimated OS rate (95% CI) at twelve (12) months was 59% (53%, 64%) in the panitumumab plus FOLFIRI arm and 53% (47%, 59%) in the FOLFIRI alone arm. Based on primary analyses, estimated OS rate (95% CI) at eighteen (18) months was 40% (35%, 46%) in the panitumumab plus FOLFIRI arm and 33% (27%, 39%) in the FOLFIRI alone arm. Subsequent chemotherapy (irinotecan, oxaliplatin, or fluoropyrimidine) was given to 160 (53%) subjects in the panitumumab plus FOLFIRI arm and 148 (50%) subjects in the FOLFIRI alone arm. Subsequent anti-EGFR therapy was received by 38 (13%) subjects in the panitumumab plus FOLFIRI arm and 101 (34%) subjects in the FOLFIRI alone arm. The median time to subsequent chemotherapy was 10.9 months in the panitumumab plus FOLFIRI arm and 7.8 months in the FOLFIRI alone arm. The median time to anti-EGFR therapy was 12.4 months (panitumumab plus FOLFIRI) and 7.9 months (FOLFIRI alone). The role of subsequent anti-EGFR therapy or chemotherapy on the estimated OS treatment effect is unknown.
The objective response rate was 36% for patients receiving panitumumab plus FOLFIRI and 10% for patients receiving FOLFIRI alone. The odds ratio for objective response was 5.50 (95% CI: 3.32, 8.87), favouring the panitumumab plus FOLFIRI arm. Stabl |
