Epidermal growth factor receptor antagonists appear poised to be the next class of targeted therapies for cancer, attracting both investor and public visibility for companies nearing the milestone of an NDA filing. But even though there are two clear frontrunners in the race to reach the market first, retaining that advantage could prove to be difficult.

The large number of cancers that may be amenable to treatment with the inhibitors is large enough to provide room for multiple marketed products, and at least six EGFr antagonists are in clinical development.

In addition, there almost certainly will be differences in survival benefit conferred by different products depending on their mode of action, which is different between the small molecule kinase inhibitors and the anti-EGFr antibodies. And differences in side effect profiles and route of administration will affect clinical use. Being first to market, whether based on survival or tumor response data, will provide an opportunity for one company to try to dominate, but a large marketing force will be required to take advantage of that edge.

Thus the EGFr data presented at last week's American Society of Clinical Oncology meeting in San Francisco marks only a stepping stone in development of this therapeutic approach, as post-regulatory decisions by clinicians will determine how market share is divided among the candidate products.

The biological rationale

EGFr belongs to a family of four epithelial cell surface receptors known as the erbB family. In addition to EGFr (erbB1), erbB2 (Her-2), which is overexpressed in some breast cancers, already has been validated as a target by Genentech Inc.'s Herceptin. The other family members are erbB3 and 4.