Increasing chemotherapeutic and targeted drug options has led to improved overall survival in metastatic colorectal cancer. Panitumumab is a fully humanized monoclonal antibody that binds to the EGF receptor and inhibits downstream cell signaling with net effects

Colorectal cancer (CRC) is the third most common cancer in men and second most common cancer in women worldwide [1]. Approximately 20% of patients will present with metastatic disease while many others with stage II or III disease will relapse with distant metastatic disease after primary treatment. The availability of active chemotherapy agents, fluoropyrimidine (oral and IV), oxaliplatin and irinotecan, has resulted in improvement in median overall survival (OS) in metastatic (mCRC) from 12 months to 18–21 months [2]. Despite this, 5-year survival for patients with mCRC remains less than 10% [3,4]. Increased adoption of metastatectomy for liver-limited disease has significantly improved long-term survival in this subset of patients with reported 5-year OS of 37–58% [5,6]. The other major advance is the recent availability of targeted therapies, targeting VEGF and EGF receptor (EGFR). Bevacizumab (Avastin, F. Hoffmann-La Roche Ltd, Basel, Switzerland), a monoclonal antibody (MoAb) targeting VEGF, prolongs progression-free survival (PFS) and OS when used in the firstand second-line of treatment in combination with chemotherapy [4]. Aflibercept (Zaltrap, Sanofi US, Inc.), also targeting VEGF, was approved by the US FDA in August 2012 for second-line treatment of mCRC in combination with infusional 5-fluorouracil (5-FU)/folinic acid/irinotecan (FOLFIRI) chemotherapy after demonstrating improved PFS and OS in this setting [7]. Regorafenib, an oral inhibitor of angiogenic signaling (including VEGF) has demonstrated improved OS and PFS as monotherapy in treatment refractory mCRC [8]. US FDA approval of regorafenib in September 2012 provides a further treatment option for patients who have exhausted all other available therapies. There are two EGFR inhibitors available on the market; cetuximab (Erbitux, Merck KgaA, Darmstadt, Germany) and panitumumab (Vectibix, Amgen Inc., CA, USA). Both drugs have demonstrated efficacy in patients with wild-type (WT; i.e., non-mutated) KRAS tumors (KRAS WT) as monotherapy in chemotherapy-refractory mCRC and in earlier lines of treatment in combination with chemotherapy. Availability and approved indications of EGFR inhibitors varies around the world based on the differing assessments of trial data by funding bodies. With the availability of new drugs, particularly targeted agents, the overall treatment algorithm for mCRC has become increasingly complex. There is a paucity of randomized trial data to assist the clinician on the best sequencing and combination of these agents. Until further trials are reported, clinicians need an understanding of the data relating to each agent to assist treatment decisions with the goal of maximizing survival and maintaining quality of life (QoL) for patients with mCRC. Christopher M Hocking1, Amanda R Townsend1 and Timothy J Price*1,2