A novel drug still in early clinical trials, GDC-0449, appears highly effective in shrinking large basal cell skin cancer with limited side effects. These results were recently presented at a late-breaking session at the 2008 Annual Meeting of the American Association for Cancer Research.

Basal cell carcinoma (BCC) is a common slow-growing skin cancer that is highly curable with surgical removal. Rarely, however, BCC becomes advanced and develops into a large tumor or multiple local tumors. In such cases surgical removal can result in unfavorable cosmetic changes or disfigurement. In very rare instances, BCC can also become truly metastatic to sites such as the lung, where cure with standard therapeutic approaches remains suboptimal.

GDC-0449 is a novel agent that provides anticancer responses by inhibiting the hedgehog pathway. The hedgehog pathway contains proteins that are involved in tissue repair and cellular growth. In BCC specific mutations are often present within the hedgehog pathway that ultimately result in excessive growth of basal cells. As a result a therapeutic approach that inhibits the mutated pathway, such as GDC-0449, halts the excessive growth of BCC cells.

Researchers from Arizona recently conducted a Phase I clinical trial to evaluate oral GDC-0449 in the treatment of nine patients with multifocal or metastatic BCC.

• Response or stabilization of the cancer was achieved in eight of the nine patients.
• In five patients with metastatic BCC to the lung, two had a partial response, two had stable disease, and one had progressive disease.
• In four patients with locally advanced or multifocal disease, two had a complete response and two had improvement.
• The median duration of time that GDC-0449 provided responses was more than 176 days.
• Side effects were reported as mild.

The researchers concluded that GDC-0449 appears to provide promising activity for patients with advanced BCC with minimal side effects.  Although this was a small, early-phase clinical trial, the results warrant further investigation of this agent.

Comments: These are impressive results in a disease where very little has been published about systemic therapy. Metastatic BCC is very rare and there are no recent data on how this disease responds to chemotherapy.

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Reference: Von Hoff D, et al. Efficacy data of GDC-0449, a systemic hedgehog pathway antagonist, in a first-in-human, first-in-class Phase I study with locally advanced, multifocal or metastatic basal cell carcinoma patients. Proceedings from the 2008 Annual Meeting of the American Association for Cancer Research (AACR).  Abstract LB-138.