Chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer: Cetuximab versus Panitumumab

The anti-EGFR monoclonal antibodies Panitumumab ( Vectibix ) and Cetuximab ( Erbitux ) are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer.
A study has assessed the efficacy and toxicity of Panitumumab versus Cetuximab in these patients.

For this randomised, open-label, phase 3 head-to-head study, researchers enrolled patients ( from centres in North America, South America, Europe, Asia, Africa, and Australia ) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group ( ECOG ) performance status of 2 or less, and wild-type KRAS exon 2 status.

Using a computer-generated randomisation sequence, researchers assigned patients ( 1:1; stratified by geographical region and ECOG performance status, with a permuted block method ) to receive Panitumumab ( 6 mg/kg once every 2 weeks ) or Cetuximab ( initial dose 400 mg/m2; 250 mg/m2 once a week thereafter ).

The primary endpoint was overall survival assessed for non-inferiority ( retention of 50% or more of the Cetuximab treatment effect; historical hazard ratio [ HR ] for Cetuximab plus best supportive care versus best supportive care alone of 0.55 ).
The primary analysis included patients who received one or more dose of Panitumumab or Cetuximab, analysed per allocated treatment. Recruitment for this trial is closed.

During the period 2010-2012, a total of 1010 patients was enrolled and randomly allocated, 999 of whom began study treatment: 499 received Panitumumab and 500 received Cetuximab.

For the primary analysis of overall survival, Panitumumab was non-inferior to Cetuximab ( Z score −3.19; p=0.0007 ). Median overall survival was 10.4 months with Panitumumab and 10.0 months with Cetuximab ( HR=0.97 ).
Panitumumab retained 105.7% of the effect of Cetuximab on overall survival seen in this study.

The incidence of adverse events of any grade and grade 3-4 was similar across treatment groups. Grade 3-4 skin toxicity occurred in 62 ( 13% ) patients given Panitumumab and 48 ( 10% ) patients given Cetuximab.
The occurrence of grade 3-4 infusion reactions was lower with Panitumumab than with Cetuximab ( 1 [ less than 0.5% ] patient vs 9 [ 2% ] patients ), and the occurrence of grade 3-4 hypomagnesaemia was higher in the Panitumumab group ( 35 [ 7% ] vs 13 [ 3% ] ).

One treatment-related fatal adverse event ( lung infection in a patient given Cetuximab ) was recorded.

The findings have shown that Panitumumab is non-inferior to Cetuximab and that these agents provide similar overall survival benefit in this population of patients.
Both agents had toxicity profiles that were to be expected.
In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 3-4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment. ( Xagena )

Price TJ et al, The Lancet Oncology 2014; 15: 569-579


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