Document Type

Article

Publication Date

9-18-2025

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This article is the author’s final published version in British Journal of Dermatology, Volume 193, Issue 4, 2025, Pages 758-766.

The published version is available at https://doi.org/10.1093/bjd/ljaf205. Copyright © The Author(s) 2025.

Abstract

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.

OBJECTIVES: To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced and/or metastatic SCCs whose disease had not previously responded successfully to standard care.

METHODS: Using a common protocol, patients were offered either oral or intravenous (IV) administration of rigosertib with consultation from the treating physician. Patients were monitored with clinical photography, biopsy, positron emission tomography/computed tomography scans and quality of life (QoL) questionnaires over the 12-month duration of the trial. The pharmacokinetics of drug absorption was monitored in four patients.

RESULTS: Antitumour efficacy with acceptable toxicity was seen in patients on IV or oral therapy and two patients had a complete response within 6 months of treatment. Their QoL was not negatively impacted by treatment and drug absorption exceeded that seen in previous patient populations presumably due to the relatively high dosing in a cohort of underweight patients.

CONCLUSIONS: These data identify rigosertib as a promising drug therapy for patients with RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumours arise on a background of a unique fibrotic and inflammatory environment -characterized by germline mutations in COL7A1 that promote the development of homogenous primary tumours with aberrant PLK1 -activity.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
Supplementary data.zip (2538 kB)

PubMed ID

40439508

Language

English

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