HDAC Inhibitor Remetinostat Associated With Positive Clinical Outcomes in Patients With Basal Cell Carcinoma

Remetinostat showed signs of clinical efficacy in patients with basal cell carcinoma (BCC), according to a study published in Clinical Cancer Research. Rementinostat, a topical cream, is a first-in-class inhibitor of histone deacetylation.

BCC is the most common form of skin cancer and is typically treated with surgical excision. However, excision can be a costly and burdensome treatment, especially for patients with multiple BCC lesions, according to the study. Topical creams can act as an alternative strategy, but only the superficial subtype of BCC is treated by the currently existing topical therapies.

The investigators previously identified histone deacetylase (HDAC) inhibition as a promising therapeutic approach for BCC, and remetinostat is an HDAC inhibitor designed to lose potency once it is absorbed beyond the skin. In this way, the drug’s activity is localized to the skin lesion in contrast with systemic HDAC inhibitors, which are associated with various toxicities.

To test remetinostat for the treatment of BCC, the investigators enrolled 30 patients with at least 1 BCC measuring 5 mm or greater in diameter at diagnosis. Participants applied remetinostat gel to their tumors 3 times per day over the course of 6 weeks.

After 8 weeks, remaining tumors were surgically removed and examined histologically. Ninety percent of participants identified as non-Hispanic white, with nearly 50% reporting a prior history of skin cancer. The majority of tumors had either nodular or superficial histology, and these tumors were found both in sun-exposed and non-exposed parts of the body.

Thirty-three tumors were included in the final analysis, 69.7% of which responded to topical treatment, including 17 complete responses and 6 partial responses. Tumor diameter decreased by 62.3% on average, and tumor area decreased by 71.5%.

“While further research is needed, our results suggest that remetinostat could be a safe and promising alternative to surgical treatment of BCC due to the high rate of complete responses we observed,” said Kavita Sarin, MD, PhD, associate professor of dermatology at Stanford University, in a press release. “However, if a therapy is to replace surgical treatment, it needs to not only induce a complete response, but also a durable one.”

Multiple BCC subtypes were observed to respond to remetinostat. The response rate among the 6 superficial BCC tumors was 100%, with 5 complete responses and 1 partial response. Nodular BCCs had a 68.2% response rate and infiltrative BCCs had a 66.7% response rate. No response was observed in the 2 micronodular tumors. Future studies will analyze the longevity of these responses.

REFERENCE

First-in-class histone deacetylase inhibitor gel shows promise for the treatment of patients with basal cell carcinoma [news release]. EurekAlert; August 6, 2021. Accessed August 6, 2021. https://www.eurekalert.org/news-releases/924444