Cetuximab-based therapy in elderly comorbid patients with metastatic colorectal cancer

Even though significant advances in the treatment of colorectal cancer (CRC) were made in the last decade with combination chemotherapy, including fluorouracil, irinotecan and oxaliplatin, CRC remains the second most leading cause of cancer-related death in the United States and western Europe (Ries et al, 2010). The development of new therapeutic agents, which target specific molecular events in tumour cells, provide new opportunities to improve treatment of this type of cancer (Imai and Takaoka, 2006). One such agent is the epidermal growth factor receptor (EGFR)-targeted IgG monoclonal antibody cetuximab (Erbitux; Merck, Darmstadt, Germany). Cetuximab interacts with the extracellular domain of EGFR, thereby partially occluding the ligand-binding region, and sterically preventing the receptor from modulating conformation required for dimerisation and active signalling. Furthermore, it is suspected that an antitumour, antibody-dependent, cell-mediated cytotoxic reaction is triggered (Li et al, 2005; Zhang et al, 2007). The efficacy of cetuximab was shown in various studies like the multinational EPIC, the BOND and the MABEL study in the irinotecan-refractory setting of pretreated metastatic colorectal cancer (mCRC). In the EPIC trial involving 1298 patients (pts) after oxaliplatin-based chemotherapy, cetuximab added to irinotecan vs irinotecan alone significantly improved progression-free survival (PFS) (median, 4.0 vs 2.6 months) and quality of life analysis (P=0.047) (Sobrero et al, 2008). In the Bond trial (329 pts), the combination of cetuximab plus irinotecan showed an improved response rate (RR) of 23% and a prolonged time to progression (TTP) of 4.1 months compared with cetuximab monotherapy (RR 10.8% and TTP 1.5 months) in irinotecan-refractory pts (Cunningham et al, 2004). Consistent with these findings, the MABEL study (1147 pts) demonstrated, in a wider standard community practice setting, similar efficacy and safety with a RR of 20% and a median overall survival of 9.2 months in pts whose mCRC had progressed on irinotecan-based chemotherapy when treated with Cetuximab in combination with a irinotecan-based chemotherapy (Wilke et al, 2008). Both studies included mainly pts with a good performance status (ECOG 0–1) and a median age in the Bond trial of 59 years and of 62 years in the MABEL study. In our experience, these pts do not represent the usual population at such advanced stage and line of pretreatment of mCRC in standard general practice. This German non-interventional study (NIS) evaluated the efficacy and safety of cetuximab in combination with chemotherapy in pretreated mCRC in pts with reduced performance status and aged >65 years.