Panitumumab is a fully humanized antibody against the EGFR. The U.S. Food and Drug Administration approved panitumumab for use in patients with metastatic colorectal cancer refractory to chemotherapy. In clinical trials, panitumumab demonstrated efficacy as a single agent or in combination therapy, which was consistent with the effects on PFS and OS with cetuximab. There appears to be a consistent class effect.
In a phase III trial, patients with chemotherapy-refractory colorectal cancer were randomly assigned to panitumumab or best supportive care.
Patients receiving panitumumab experienced an improved PFS (8 weeks vs. 7.3 weeks, HR, 0.54; 95% CI, 0.44–0.66; P < .0001).[Level of evidence: 1iiDiii]
There was no difference in OS, which was thought to be the result of 76% of patients on best supportive care crossing over to panitumumab.
In the PRIME (NCT00364013) study, 1,183 patients were randomly assigned to FOLFOX4 with or without panitumumab as first-line therapy for metastatic colorectal cancer. The study was amended to enlarge the sample size to address patients with the KRAS wild-type tumors and patients with mutant KRAS tumors separately.
For patients with KRAS wild-type tumors, a statistically significant improvement in PFS was observed in those who received panitumumab/FOLFOX4 compared with those who received only FOLFOX4 (HR, 0.80; 95% CI, 0.66–0.97; P = .02, stratified log-rank test).[Level of evidence: 1iiDiii]
Median PFS was 9.6 months (95% CI, 9.2 months–11.1 months) for patients who received panitumumab/FOLFOX4 and 8.0 months (95% CI, 7.5 months–9.3 months) for patients who received FOLFOX4. OS was not significantly different between the groups (HR, 0.83; 95% CI, 0.67–1.02; P = .072).
For patients with mutant KRAS tumors, there was worse PFS with the addition of panitumumab (HR, 1.29; 95% CI, 1.04–1.62; P = .02, stratified log-rank test).
Median PFS was 7.3 months (95% CI, 6.3 months–8.0 months) for panitumumab/FOLFOX4 and 8.8 months (95% CI, 7.7 months–9.4 months) for FOLFOX4 alone.
Similarly, the addition of panitumumab to a regimen of FOLFOX/bevacizumab resulted in a worse PFS and worse toxicity compared to a regimen of FOLFOX/bevacizumab alone in patients not selected for KRAS mutation in metastatic colon cancer (11.4 months vs. 10.0 months, HR, 1.27; 95% CI, 1.06–1.52).[Level of evidence: 1iiDiii]
In another study (NCT00339183), patients with metastatic colorectal cancer who had already received a fluoropyrimidine regimen were randomly assigned to either FOLFIRI or FOLFIRI plus panitumumab.
In a post hoc analysis, patients with KRAS wild-type tumors experienced a statistically significant PFS advantage (HR, 0.73; 95% CI, 0.59–0.90; P = .004, stratified log-rank).[Level of evidence: 1iiDiii]
Median PFS was 5.9 months (95% CI, 5.5 months–6.7 months) for panitumumab/FOLFIRI and 3.9 months (95% CI, 3.7 months–5.3 months) for FOLFIRI alone.
OS was not significantly different. Patients with mutant KRAS tumors experienced no benefit from the addition of panitumumab.