First-in-Class Gel Shows Promise for Basal-Cell Carcinoma

NEW YORK (Reuters Health) – A first-in-class topical histone deacetylation (HDAC) inhibitor has shown promise in the treatment of basal-cell carcinoma, the most common form of skin cancer.

“Our study was a proof-of-principle study that demonstrated that a topical HDAC inhibitor can shrink the majority of basal cell cancers and lead to complete resolution in half of them,” Dr. Kavita Sarin of Stanford University in California told Reuters Health by email.

“The ultimate goal is to develop a topical therapy that can replace surgery for the majority of patients with basal-cell cancer. For this to be achieved, we need a therapy that is well-tolerated, highly effective, and durable, meaning that the basal-cell cancer does not recur after the therapy is discontinued. A topical therapy would enable patients to avoid the scarring and morbidity of surgical excision,” said Dr. Sarin.

In this phase-2 clinical trial, Dr. Sarin and colleagues evaluated the safety and efficacy of the topical HDAC inhibitor remetinostat in 30 adults (median age, 59 years; 63% male), each with at least one BCC measuring 5 mm or greater in diameter at diagnosis.

Eight patients had multiple eligible tumors for a total of 49 tumors in the study.

The tumors were located in both sun-exposed and non-exposed parts of the body, and most had either nodular or superficial histology.

All patients applied 1% remetinostat gel to their tumors three times daily for six weeks. After eight weeks, any remaining tumor was surgically removed and examined histologically.

The final analysis was based on 33 tumors from 25 participants.

The overall response rate – defined as the proportion of tumors with greater than 30% decrease in the longest diameter from baseline to week eight – was 69.7%, with 17 complete responses and six partial responses.

On average, tumor diameter decreased by 62.3% and tumor area decreased by 71.5%, the study team reports in Clinical Cancer Research.

Two tumors had no change in diameter, while eight tumors decreased in size but by less than the 30% threshold for partial response. No tumors increased in diameter.

Multiple BCC subtypes responded to topical remetinostat; all six superficial BCC tumors responded (five complete and one partial response), while the response rate was 68.2% among 22 nodular BCCs (10 complete and five partial responses) and 66.7% among three infiltrative BCCs (two complete responses). No responses were seen in the two tumors of micronodular subtype.

The gel was well tolerated with no systemic or serious adverse events reported. The most common adverse event was an eczema-like skin reaction at the site of application.

Dr. Sarin cautioned that, in this study, all tumor sites were excised shortly after the end of treatment.

“We need to conduct a durability study to understand whether the BCC tumors regrow after treatment if they are not excised. A durable tumor response is critical in order for a therapy to replace surgical excision. We also need to optimize dosing, treatment times, and application methods to maximize efficacy,” Dr. Sarin told Reuters Health.

This was an investigator-initiated study supported by Medivir AB, Sweden, which is developing remetinostat. Other support was provided by Damon Runyon Foundation, the National Cancer Institute, National Institutes of Health (NIH), American Skin Association and Stanford Medical Scholars. Several authors disclosed relationships with Medivir.

SOURCE: Clinical Cancer Research, online August 6, 2021.

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