The evidence supporting this regimen comes from a multicenter, randomised phase III trial comparing panitumumab plus best supportive care (BSC) versus BSC alone. The study was not blinded because of the expected skin toxicity related to panitumumab.r
Between January 2004 to June 2005, 463 patients were enrolled in the study, 231 randomised to panitumumab and 232 to BSC.
The primary end point was progression-free survival secondary end points were objective response rate and overall survival.
Results from the ASPECCT trial (n=999) has shown that single agent panitumumab was non inferior to cetuximab in extending overall survival (OS) in patients with chemorefractory KRAS wild-type metastatic colorectal cancer. However, for patients who progress on panitumumab, there is currently no data to support switching to cetuximab.r
Monoclonal antibodies (mABs) targeting the epidermal growth factor receptor (EGFR) prolong survival in patients with metastatic colorectal cancer (mCRC) harbouring KRAS exon 2 wild type tumours. Recent evidence suggest that other RAS mutations (exon 3 and 4 of KRAS and exons 2, 3, 4 of NRAS) may also be predictive of resistancer, r and many studies suggest that anti-EGFR mAB treatment may have a detrimental effect on PFS and OS in patients with NRAS mutations.r As such, panitumumab should not be used in patients with any RAS mutations.
The median PFS was identical between the Panitumumab and the BSC care arm however there was a statistically significant improvement in the mean PFS (13.8 weeks compared with 8.5 weeks). The changes in PFS in this context should be interpreted with caution as 76% of patients crossed over from the BSC arm to panitumumb and in most cases this occurred prior to the first assessment at week 8. There was no change in overall survival.r
A post hoc analysis of the patients according to the KRAS status of their tumour showed that patients in the panitumumab group with wild type tumours had a median PFS of 12.3 weeks compared with 7.4 weeks for those with KRAS mutant cancers. The median PFS for the BSC group was 7.3 weeks irrespective of the KRAS status of the tumour. The improvement in PFS survival in the KRAS wild-type group did not translate into an improvement in overall survival.r
PFS and HR for panitumumab vs BSC in wild-type KRAS patientsr
© Journal of Clinical Oncology 2008
As with most EGFR inhibitors, skin-related toxicities were more common in the panitumumab group (90% versus 9%).r
Hypomagnesia was another common side effect in the panitumumab group (36% versus 1%).r
19% of patients in the panitumumab group had a grade 3 (severe) treatment-related adverse event compared with 0 in the BSC arm.r
© Journal of Clinical Oncology 2007
By maximum grade and by KRAS group, there was an increased risk of grade 3 or 4 adverse events in patients receiving panitumumab who have the wild type KRAS tumours (44%) compared to those with mutant KRAS tumours (28%).r
||wild type KRAS
|Skin toxicity (grade 3)
|Diarrhoea (any grade)
|Hypomagnesia (any grade)