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Topical Remetinostat Effective, Tolerable in Basal Cell Carcinoma


The topical HDAC inhibitor remetinostat demonstrated favorable tolerability and clinically significant efficacy in reducing disease burden in patients with basal cell carcinoma, according to results from a phase 2 trial.

The topical HDAC inhibitor remetinostat demonstrated favorable tolerability and clinically significant efficacy in reducing disease burden in patients with basal cell carcinoma, according to results from a phase 2 trial (NCT03180528) published in Clinical Cancer Research.1

Results from the study showed an overall response rate (ORR) of 69.7% (90% CI, 54%-82.5%), which was defined as the proportion of tumors that achieved a decrease in diameter of at least 30% from baseline to week 8. Additionally, 54.8% of tumors demonstrated complete resolution, and no systemic adverse effects (AEs) were reported.

“Although 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,” Kavita Sarin, MD, PhD, senior author of the study and an associate professor of dermatology at Stanford University, stated in a press release.2

Basal cell carcinoma is the most common cancer worldwide, and surgery continues to be the standard of care. Surgical procedures, however, are time consuming and costly, resulting in nearly $4 billion in annual healthcare costs in the United States alone; they have also been associated with cosmetic and functional morbidity. As such, there is an unmet need for non-surgical approaches for this patient population.

Remetinostat is an HDAC inhibitor that has been shown to retain potency within the skin, but also metabolize upon absorption and produce effective local activity in cutaneous lesions. Additionally, the agent has been previously studied in patients with cutaneous T-cell lymphoma with no treatment-related systemic AEs reported.

As such, investigators sought to examine the safety and efficacy of topical 1% remetinostat gel in patients with basal cell carcinoma.

Patients on the study were instructed to apply the remetinostat gel 3 times daily for 6 weeks. Measurements of tumor diameter were conducted at baseline, as well as after 8 weeks of treatment. Surgical excision of the remaining tumor was done at the end of the study period.

To be eligible for enrollment, patients had to have at least 1 cutaneous basal cell carcinoma that was 5 mm in diameter or larger and be amenable to surgical resection. Additionally, women enrolled to the study were required to show proof of a negative pregnancy test and use contraceptives while on the study. Those with lesions larger than 25 mm that were cosmetically sensitive, inoperable, locally advanced, or metastatic were excluded.

Secondary outcomes included change in tumor cross-sectional area, pathologic resolution of the tumor at time of excision, participant compliance, relative change in GLI1 mRNA expression, and the incidence, nature, and severity of AEs.

A total of 30 participants with 49 basal cell carcinoma tumors were enrolled to the study between May 2018 and June 2020. Of those participants, 25 patients with 33 tumors were included in the per-protocol analysis.

The median age of patients enrolled to the study was 59 years (range, 38-86), and the majority were male (63%) and White (90%). Additionally, 47% of patients had a prior history of skin cance were enrolled with just 1 basal cell carcinoma tumor. Moreover, most tumors were either nodular (35%) or superficial (14%) in histology.

Additional data showed that from baseline to week 8, 6 partial responses (PRs) were reported with the approach, along with 17 complete responses in the tumor longest diameter. Moreover, the average change in the longest tumor diameter was a 62.3% decrease. Of the 33 tumors examined in the per-protocol analysis, 2 did not change in diameter and 8 decreased in size but less than the 30% threshold for a PR. Notably, no tumors increased in diameter.

Based on histology, those with superficial basal cell carcinoma tumors responded the best to treatment, with an ORR of 100%. Moreover, those with nodular tumors experienced an ORR of 68.2%, and those with infiltrative tumors reported an ORR of 66.7%. The micronodular subtype did not respond to treatment.

Additionally, age under 60 years, male gender, and a history of prior skin cancer were all linked with small, non-significant increases in ORR. Tumor location on a sun-exposed site and higher grade of cutaneous drug reaction were both linked with larger ORRs, although these increases were still not determined to be of statistical significance. The ORR in those with sun-exposed sites was 81.8% vs 63.6% in those with nonexposed sites. In those with grade 2 to 3 cutaneous drug reaction, the ORR was 73.9% vs 60.0% in those with grade 1 or no reaction.

Moreover, the average change in tumor area was a decrease of 71.5%.

Ninety percent of patients experienced at least 1 AE. The most frequently reported AE was an eczematous reaction localized to the site of drug application. A total of 27 discrete episodes were reported, with a mean duration of 64.4 days. Most of these cases were grade 2 in severity (n = 21), 5 were grade 1, and 1 was grade 3. Additionally, 4 patients had to suspend treatment due to an eczematous reaction, and 3 patients stopped treatment permanently because of this toxicity.

A less frequently reported AE was pain at the site of drug application, and 6 episodes were reported; 4 of these episodes were grade 1 and 2 were grade 2. Two participants had to temporarily suspend treatment.

“Given the tolerability and clinical and pathologic response rates demonstrated in this trial across several histological subtypes, HDAC inhibitors could be a realistic new class of topical agents for basal cell carcinoma,” the study authors wrote. “In patients suffering from recurrent disease, an effective topical treatment could have a revolutionary impact on patient outcomes, morbidity and quality of life, and for this reason, further trials are warranted, particularly to assess the durability of treatment response following HDAC inhibitor therapy.”

This article was initially published by our sister publication Onc Live.


  1. Kilgour JM, Shah A, Urman NM, et al. Phase II open-label, single-arm trial to investigate the efficacy and safety of topical remetinostat gel in patients with basal cell carcinoma. Clin Cancer Res. Published online August 6, 2021. doi:10.1158/1078-0432.CCR-21-0560
  2. First-in-class histone deacetylase inhibitor gel shows promise for the treatment of patients with basal cell carcinoma. News release. AACR. August 6, 2021. Accessed August 25, 2021. https://bit.ly/38ds8ct
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