Panitumumab
Vectibix (Amgen)
vials containing 20 mg/mL in 5 mL, 10 mL or 20 mL volume
Approved indication: metastatic colorectal carcinoma
Australian Medicines Handbook section 14.2.1Panitumumab is a humanised monoclonal antibody for the treatment of metastatic colorectal carcinomas expressing the epidermal growth factor receptor. It is indicated for patients whose tumours have progressed after fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy.
This antibody prevents the growth of tumour cells and causes cell death by binding to the epidermal growth factor receptor and competitively inhibiting autophosphorylation induced by various ligands such as epidermal growth factor and transforming growth factor-alpha. Antibody binding also decreases the production of interleukin-8 and vascular endothelial growth factor.Panitumumab is given as an intravenous infusion. The pharmacokinetics of this drug vary depending on the dose, with clearance decreasing at higher doses. Steady state is reached after three doses of 6 mg/kg once a fortnight. The mean half-life during this dosing interval is approximately 7.5 days.
In an open-label phase III trial of 463 patients with progressive metastatic colorectal cancer, panitumumab with best supportive care was compared to best supportive care alone. Patients were given panitumumab until their disease progressed or they died. Although the median progression-free survival time with panitumumab was similar to the control (8 vs 7.3 weeks), the mean progression-free survival for panitumumab was 5 weeks longer (13.8 vs 8.5 weeks). There was no difference in overall survival between the groups.1
The efficacy of panitumumab seems to be confined to a subset of patients with tumours expressing the wild-type (non-mutated) KRAS gene (Kirsten rat sarcoma-2 virus oncogene). Following further analysis of the phase III trial, the median progression-free survival was 12.3 weeks in patients with wild-type KRAS and 7.4 weeks in those with mutant KRAS, after receiving panitumumab. There was no difference in overall survival between the groups.2 In total, 43% of patients in the trial were found to have KRAS mutations so this is an important factor to consider when selecting patients for panitumumab therapy.
Although panitumumab benefits some patients, it causes considerably more adverse events than supportive care alone. Skin-related toxicity is the most common adverse effect, affecting over 90% of patients. Erythema, acneiform dermatitis, pruritus, skin exfoliation, paronychia, rash and skin fissures have been reported.1 (The likely cause of these reactions is inhibition of epidermal growth factor receptor in the basal layers of the skin.) Eye-related toxicities and stomatitis have also been observed with this drug. Patients should be monitored for inflammatory and infectious conditions associated with skin toxicity. Sunlight can exacerbate skin reactions so protection from the sun is recommended.
Health professionals should be aware that panitumumab has been associated with an increased risk of venous thromboembolic events. In the phase III trial, 12 of 231 patients had a thromboembolic event.1 One case of pulmonary embolism with panitumumab was fatal and two were life threatening.
Almost 40% of patients who received panitumumab developed hypomagnesaemia, 5% of which were serious, so patients should be regularly monitored during and for eight weeks after completion of therapy. Gastrointestinal problems were more common with panitumumab than with the control treatment.1
So far, adding panitumumab to chemotherapy treatments does not appear to give clear benefits. Severe diarrhoea was reported by 58% of patients who received panitumumab in combination with fluorouracil, leucovorin and irinotecan. As diarrhoea can exacerbate electrolyte depletion, this combination of drugs should be avoided. In another trial, adding panitumumab to oxaliplatin- and irinotecan-based chemotherapy and bevacizumab resulted in increased toxicity without improving efficacy.
Although the benefits seem marginal, panitumumab does offer another option for patients who have not responded to standard chemotherapy. It is not known how panitumumab compares with cetuximab, another inhibitor of the epidermal growth factor receptor, for the treatment of colorectal cancer.
Before starting treatment it is important to first ascertain that the patient’s tumour is expressing epidermal growth factor receptor. Expression of the wild-type KRAS gene may improve a patient’s response to panitumumab. However, these findings are still preliminary and need to be confirmed in further studies.
References*†
manufacturer provided only the product information
1. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 2007;25:1658-64.2. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:1626-34.
Source: Australian Prescriber. New drugs: Panitumumab. Volume 31 Number 5 – October 2008