according to research presented at the annual meeting of the Society for Investigative Dermatology.
“Our results demonstrate a clinically significant decrease in tumor size in response to 6 weeks of topical 1% remetinostat therapy in 70% of per-protocol tumors, with 55% reaching complete pathological resolution,” James M. Kilgour, MD, a postdoctoral research fellow at the Sarin Lab at Stanford (Calif.) University, said at the meeting.
Surgical excision is the preferred treatment for BCC, but there is still a need for noninvasive treatment options, Dr. Kilgour said. “Given the potential morbidity associated with excision, particularly for patients experiencing multiple or recurrent tumors, such as the immunosuppressed or patients with Gorlin syndrome, an effective and tolerable topical therapy would be a significant benefit,” he noted.
Previously, in an in silico screen experiment, Dr. Kilgour and colleagues identified HDAC inhibitors as a “top predicted therapeutic” for BCC treatment, and found that in mice studies, HDAC inhibitors were able to suppress the growth of BCC cell lines and BCC allografts.
Remetinostat, a pan-HDAC inhibitor, is being investigated as a treatment for cutaneous T-cell lymphoma.
HDAC inhibitors are thought to “alter expression of key oncogenes and tumor suppressors through epigenetic modification of histone and nonhistone proteins,” he noted.
To evaluate the efficacy of topical remetinostat for BCC, the investigators enrolled 30 patients with 49 BCC tumors in a phase 2, open-label, single-arm trial. Participants had tumors that were greater than 5 mm in diameter and had been referred to surgery at Stanford before enrollment. Patients were a mean of 59 years old, 63% were men, and 90% were White; 59.2% of participants had tumors with a diameter greater than 10 mm, the rest had tumors with a diameter of 10 mm or less.
After the tumors were photographed and measured, participants received 6 weeks of topical remetinostat therapy, followed by final measurement and photography of the tumors at 8 weeks and surgical excision. Topical remetinostat 1% gel was applied three times per day under bandage occlusion.
Overall, 25 participants with 33 tumors were included in the per-protocol analysis. At 8 weeks, there was at least a 30% decrease in diameter from baseline for 69.7% of tumors in these patients, with 17 of 33 tumors showing a complete response by week 8.
Regarding tumor subtypes, there was a 100% overall response rate for the 6 superficial BCC tumors (1 partial response, 5 complete responses), a 68.2% ORR for the 22 nodular tumors (5 partial responses, 10 complete responses), and a 66.7% ORR for the 3 infiltrative tumors (no partial responses, 2 complete responses). There were no partial or complete responses for the two micronodular tumors.
Most adverse events in the study were localized drug reactions, with no serious or systemic adverse events, Dr. Kilgour noted, with 10 tumors demonstrating either no reaction or a grade 1 reaction, and 23 tumors having a grade 2 or grade 3 response.
The investigators also used imaging (ImageJ) software to evaluate the average decrease in cross-sectional tumor area. The results of the analysis showed an average decrease at 8 weeks from baseline of 71.5%. In addition, histological assessment at 8 weeks demonstrated that 54.8% of tumors had complete pathological resolution.
“In the future, we advocate for a follow-up blinded, randomized, controlled trial of remetinostat with greater participant diversity,” Dr. Kilgour said. “Specifically, greater power is needed to understand which histological subtypes of BCC will respond best to the treatment and we need to understand the long-term durability of tumor resolution.”