Rigosertib Shows Promise in EB-Associated Skin Cancer

TOPLINE:

Rigosertib, a polo-like kinase 1 (PLK1) inhibitor, demonstrated antitumor efficacy in patients with recessive dystrophic epidermolysis bullosa (RDEB) and advanced squamous cell carcinoma (SCC), with an objective response achieved in four of five patients.

METHODOLOGY:

• Researchers conducted an open-label, single-arm phase 2 study in Austria and the United States of five patients with advanced, treatment-refractory RDEB-SCC who had failed prior standard of care and were then treated with oral or intravenous (IV) rigosertib.
• Participants (median age, 23 years) received either oral rigosertib (560 mg twice daily on days 1-21 of each 28-day cycle for 13 cycles) or IV rigosertib (1800 mg/24 h as a 72-h continuous infusion on days 1-3 of each 14-day cycle for eight cycles, then on days 1-3 of 28-day cycles until 1 year of treatment).
• Two patients received IV treatment, two received oral treatment, and one received a combination of both.
• The primary outcome was the objective response rate and safety. Quality of life was a secondary outcome.

TAKEAWAY:

• Two patients achieved complete a compete response, and two others had partial responses. The fifth patient discontinued treatment early because of unrelated complications.
• Rigosertib was generally well tolerated. Most adverse events were urinary-related (cystitis, hematuria) and manageable with dose adjustments or symptomatic treatment.

IN PRACTICE:

“These initial results indicate rigosertib as a promising drug therapy for RDEB-SCC where there is a substantial unmet need and no approved therapies,” the study authors wrote. The study, they noted, was the “first clinical trial of any experimental cancer therapeutic in this rare and complicated monogenic disease.”

SOURCE:

The study was led by Martin Laimer, Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria, and was published online on May 29 in British Journal of Dermatology.

LIMITATIONS:

Usefulness of imaging techniques in this study was limited, particularly because of the chronic inflammatory response in lesional skin that is inherent to RDEB.

DISCLOSURES:

The study was funded by Debra International through Debra Austria, Debra of America, Cure EB, and Debra UK. Laimer and three other authors reported receiving consulting fees and grants from Onconova Therapeutics, Inc. Two authors declared being employees of Onconova, which provided the study drug.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.