e disease was seen in 114 (38%) patients in the panitumumab plus FOLFIRI arm and 157 (55%) patients in the FOLFIRI alone arm.
The estimated mean (SD) for time to response for responding patients was 2.8 (1.6) months (panitumumab plus FOLFIRI) versus 3.3 (1.4) months (FOLFIRI alone). The duration of response was longer in the panitumumab plus FOLFIRI arm (median 7.6 months [95% CI: 6.7, 9.4]) than in the FOLFIRI alone arm (median 6.6 months [95% CI: 5.7, 10.4]). Time to disease progression was also longer in the panitumumab plus FOLFIRI arm (median 7.3 months [95% CI: 5.9, 7.5]) compared with the FOLFIRI alone arm (median 5.3 months [95% CI: 3.9, 5.7]; hazard ratio 0.683), favouring the panitumumab plus FOLFIRI arm. Eighteen (18) % (n = 115) of panitumumab patients had been exposed to prior bevacizumab treatment. PFS and Response Rate were similar regardless of prior bevacizumab treatment.
In patients with mutant KRAS mCRC (n = 486), no significant difference in PFS (HR (95% CI): 0.95 (0.78, 1.14)) and OS (HR (95% CI): 0.93 (0.77, 1.13)) was observed between treatment arms. Vectibix is indicated only for the treatment of wild-type KRAS mCRC.
First-line combination with bevacizumab and oxaliplatin or irinotecan-based chemotherapy
In a randomised, open label, controlled clinical trial, chemotherapy (oxaliplatin or irinotecan) and bevacizumab were given with and without panitumumab in the first line treatment of patients with metastatic colorectal cancer (n = 1053 [n = 823 oxaliplatin cohort, n = 230 irinotecan cohort]). Panitumumab treatment was discontinued due to a statistically significant reduction in PFS in patients receiving panitumumab observed in an interim analysis.
The major study objective was comparison of PFS in the oxaliplatin cohort. In the final analysis, the hazard ratio for PFS was 1.27 (95% CI: 1.06, 1.52). Median PFS was 10.0 (95% CI: 8.9, 11.0) and 11.4 (95% CI: 10.5, 11.9) months in the panitumumab and the non-panitumumab arm, respectively. There was an increase in mortality in the panitumumab arm. The hazard ratio for overall survival was 1.43 (95% CI: 1.11, 1.83). Median overall survival was 19.4 (95% CI: 18.4, 20.8) and 24.5 (95% CI: 20.4, 24.5) in the panitumumab arm and the non-panitumumab arm.
An additional analysis of efficacy data by KRAS status did not identify a subset of patients who benefited from panitumumab in combination with oxaliplatin- or irinotecan based chemotherapy and bevacizumab. For the wild-type KRAS subset of the oxaliplatin cohort, the hazard ratio for PFS was 1.36 with 95% CI: 1.04-1.77. For the mutant KRAS subset, the hazard ratio for PFS was 1.25 with 95% CI: 0.91-1.71. A trend for OS favouring the control arm was observed in the wild-type KRAS subset of the oxaliplatin cohort (hazard ratio = 1.89; 95% CI: 1.30, 2.75). A trend towards worse survival was also observed with panitumumab in the irinotecan cohort regardless of KRAS mutational status. Overall, panitumumab treatment combined with chemotherapy and bevacizumab is associated with an unfavourable benefit-to-risk profile irrespective of tumour KRAS mutational status.
This medicinal product has been authorised under a “conditional approval” scheme. This means that further evidence on this medicinal product is awaited, in particular data are required to confirm the effect in patients with wild-type KRAS tumours which is currently supported by a retrospective analysis. Further evidence is also awaited regarding the effect of panitumumab in combination wi |
