A small phase II study of the topical histone deacetylase (HDAC) inhibitor remetinostat in patients with basal cell carcinoma found that the therapy was well tolerated and demonstrated clinical efficacy with no systemic side effects. The findings suggest that HDAC inhibitors are likely an effective therapeutic class for cutaneous malignancies and could have potential for wider oncologic use, although additional clinical trials are needed to assess treatment response durability, according to the study authors. The results were published by Kilgour et al in Clinical Cancer Research.

Basal cell carcinoma is the most common form of skin malignancy worldwide. In the United States alone, it is estimated that each year, 4.3 million people are diagnosed with the cancer. Although the definitive treatment for basal cell carcinoma is surgical excision, these procedures can be burdensome and expensive, especially for patients with recurrent tumors.

Study Methodology

The researchers enrolled 30 adult patients diagnosed with at least one basal cell carcinoma measuring 5 mm or greater in diameter from 2018 to 2020. Eight patients had multiple eligible tumors, resulting in a total of 49 tumors in the study, with 25 participants and 33 tumors included in the final analysis.

Nearly all patients—90%—identified as non-Hispanic White, and almost half had a prior history of skin cancer. The median age of the participants was 59 years, and 63% were male. The tumors were found in both sun-exposed and nonexposed parts of the body, and the majority had either nodular or superficial histology.

All of the study participants applied 1% remetinostat gel three times a day for 6 weeks, with measurement of tumor diameter conducted at baseline and week 8. Surgical excision of the remaining tumor was conducted at the end of the study, and samples were microscopically evaluated.

Results

Of the 33 tumors from 25 participants included in the final analysis, the researchers found the overall response rate (defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8) was 69.7% (90% confidence interval [CI] = 54%–82.5%). On pathologic examination, 54.8% of the tumors demonstrated complete resolution. Pharmacodynamic analysis demonstrated similar levels of acetylated histone H3 in skin tissue before and after treatment; however, phosphorylation was increased.

No systemic adverse events were reported. The most commonly reported event was an eczema-like skin reaction at the remetinostat application site.

“The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing basal cell carcinoma disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for basal cell carcinoma,” concluded the study authors.

Translational Relevance

“While further research is needed, our results suggest that remetinostat could be a safe and promising alternative to surgical treatment of basal cell carcinoma due to the high rate of complete responses we observed,” said senior study author Kavita Y. Sarin, MD, PhD, Associate Professor of Dermatology at Stanford University, in a statement. “However, if a therapy is to replace surgical treatment, it needs to not only induce a complete response, but also a durable one.”

Dr. Sarin continued: “Our study also showed remetinostat’s clinical efficacy against nodular basal cell carcinoma, one of the more common basal cell carcinoma subtypes. An ideal therapeutic for basal cell carcinoma should treat both nodular and superficial basal cell carcinomas, and, ideally, the other subtypes as well.”

Disclosure: Funding for this study was provided by Medvir AB, the Damon Runyon Foundation, the National Cancer Institute, the American Skin Association Hambrick Medical Student Grant, and Stanford Medical Scholars. For full disclosures of the study authors, visit clincancerres.aacrjournals.org.