Oncologists attending the European Society of Medical Oncology (ESMO) meeting in Istanbul this week were told the ultimate key to choosing between the two rival epidermal growth factor receptor (EGFR) inhibitors - Merck KGaA’s Erbitux (cetuximab) and Amgen’s Vectibix (panitumumab) – will lie in how they perform in first-line treatment of metastatic colorectal cancer.

Amgen’s drug received US Food and Drug Administration (FDA) approval for third-line monotherapy use last week and is expected to receive EMEA approval within a few months. In the USA, Amgen is fighting Erbitux on a cost basis by offering a substantial discount and price-capping incentive to patients funding their own treatment.

In Europe, cost is unlikely to factor in clinical decisions. Professor Alberto Sobrero, Genova, Italy, who acted as discussant appraising three studies with Erbitux and available data on Vectibix, said Erbitux currently has the upper hand by dint of its much more extensive clinical trial programme showing how it performs synergistically with various chemotherapies in a range of clinical settings. This compares to very limited experience with Vectibix.

But, ultimately the way the two drugs perform in large trials in the first-line mCRC treatment will determine which becomes the standard, he stressed. Erbitux with six big trials in progress versus Vectibix with only two is currently the better bet, he believes. The first Phase III trial of Erbitux in first-line therapy is due to be presented at the American Society of Clinical Oncology (ASCO) GI meeting in January 2007.

In the meantime, he advised oncologists to weigh up the two biologicals on the basis of their efficacy, toxicity, pharmacokinetics and experience across a spectrum of activity.

Although both targeted therapies act on the EGFR via the same mechanism of action, each was different and had pros and cons, he said.

Erbitux, an IgG1 monoclonal antibody, has a theoretical advantage in boosting the immune system’s own cytotoxic capability. Vectibix, which is an IgG2 MAb, has no effect on this. However, Vectibix may produce fewer infusion reactions than Erbitux and its longer half-life could make it feasible to adminster at three-week intervals compared with two-weekly intervals for Erbitux. On the other hand Vectibix has revealed a potential problem with hypomagnesia and has theoretical cardiac complications, according to Sobrero.

First-line study of Erbitux + two chemo regimens

Meanwhile, this week at ESMO, Erbitux produced more promising data in first-line treatment for metastatic colorectal cancer.

A Phase II study showed Erbitux is able to boost the response and disease control rates of two chemotherapy regimens, XELIRI (capecitabine and irinotecan) and XELOX (capecitabine plus oxaliplatin). Overall response and disease control rates were 42% and 90.9% respectively in the XELIRI + Erbitux group and 65.5% and 93.1% in the XELODA + Erbitux group.

Professor Volker Heinemann of Munich University who presented the data said: “Both regimens were highly effective.” Without Erbitux the usual response and disease control rates for the two chemotherapy

regimens would be 20%-30% less. A further Phase II study of first-line Erbitux + XELOX from a Swiss group was less impressive however.

Previous data from another Phase II study ACROBAT showed first-line Erbitux alongside FOLFOX-4 producing a response rate of 81% and a disease control rate of 98%.

A late-breaking study at ESMO, EVEREST, from Professor Eric Van Cutsem of Leuven University, Belgium, showed that boosting the dose of Erbitux in patients who display only a minor skin reaction initially increased their chances of obtaining a good response to the level of patients who develop a marked skin reaction from the start.

Severity of the acneiform rash patients develop on treatment has proved a useful predictor of outcome. However Prof Van Cutsem said skin and tumour biopsies taken from EVEREST patients may pinpoint the precise mechanism that shrinks tumours whilst affecting skin more severely. This might then be exploited in future treatment strategies.

From Olwen Glynn Owen in Istanbul