U.S. Food and Drug Administration Approval: Panitumumab for Epidermal Growth Factor Receptor–Expressing Metastatic Colorectal Carcinoma with Progression Following Fluoropyrimidine-, Oxaliplatin-, and Irinotecan-Containing Chemotherapy Regimens

Abstract

Purpose: To describe the Food and Drug Administration review and marketing approval considerations for panitumumab (Vectibix) for the third-line treatment of patients with epidermal growth factor receptor^expressing metastatic colorectal carcinoma. Experimental Design: Food and Drug Administration reviewed a single, open-label, multicenter trial in which 463 patients with epidermal growth factor receptor^expressing metastatic colorectal cancer who had progressed on or following treatment with a regimen containing a fluoropyrimidine, oxaliplatin, and irinotecan were randomized (1:1) to receive best supportive care (BSC) with or without panitumumab (6 mg/kg every other week) administered until disease progression or intolerable toxicity. Progression and response were confirmed by an independent review committee masked to treatment assignment. At progression, patients in the BSC-alone arm were eligible to receive panitumumab. Results: Although median progression-free survival (PFS) was similar in both treatment arms (f8 weeks), the mean PFS was f50% longer among patients receiving panitumumab than among those receiving BSC alone (96 versus 60 days, respectively) and the objective response rate in patients receiving panitumumab was 8%. However, no difference in overall survival was shown between the two study arms. Conclusions: Panitumumab received accelerated approval based on improvement in PFS and an independently confirmed response rate of 8%, similar to that observed with other active agents at this advanced stage of disease. Confirmation of clinical benefit will be required for full approval. 5 This accelerated approval was based on the surrogate end point of tumor response. The clinical benefit (i.e., improved PFS or OS) of cetuximab in a study of 572 patients who had failed both irinotecan-and oxaliplatin-based chemotherapy regimens randomized (1:1) to receive best supportive care (BSC) with or without cetuximab administered as an i.v. infusion of 400 mg/m 2 on the first dose and then 250 mg/m 2 . Patients randomized to receive cetuximab showed a statistically 5

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients

“…Current regimens for patients with metastatic CRC include anti-EGFR monoclonal antibodies such as cetuximab and panitumumab, both functioning to block the binding of ligands to EGFR, thereby downregulating ERK/MAPK and PI3K/PTEN/AKT pathway signalling (Amado et al, 2008;Giusti et al, 2008;Segal and Saltz, 2009). New evidence suggests that patients with KRAS, BRAF or PTEN mutations experience fewer clinical responses to these drugs, compared with patients with wild-type tumours; moreover, molecular analysis, particularly of KRAS, is routinely being performed in standard molecular pathology laboratories (Lievre et al, 2006;Amado et al, 2008;Di Nicolantonio et al, 2008;Karapetis et al, 2008;Au et al, 2009;Jimeno et al, 2009;Sartore-Bianchi et al, 2009).…”

Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario

“…The efficacy of the drug in monotherapy has been demonstrated in comparison with best supportive care (BSC) in 463 mCRC patients refractory to 5-FU, irinotecan and oxaliplatin. In this trial, although no improvement in OS was obtained, panitumumab provided a significant benefit in RR (10 vs 0%; p < 0.001) and PFS at 8 weeks (49 vs 30%; p < 0.001) and further analysis confined these benefits to KRAS wild-type patients [65,66]. The use of panitumumab as first-line treatment in addition to FOLFOX chemotherapy has been evaluated in the randomised PRIME trial, the results of which showed an improvement both in median PFS for KRAS wild-type mCRC patients treated with panitumumab plus chemotherapy (10 vs 8.6 months; HR: 0.80; p = 0.01) and in median OS (23.9 vs 19.7 months; HR: 0.88; p = 0.17) [67].…”

Rash Rates with EGFR Inhibitors: Meta-Analysis

“…Three studies were excluded from the analysis: one study used an egfri in both arms 13 , one did not present rash rates according to either grades 3 and 4 criteria or allgrades criteria 14 , and one study was a duplicate of another study 15 . Thus thirteen studies were eligible for inclusion in the meta-analysis ( Table ii).…”