Ingenol Mebutate 0.06% Gel for Field Treatment of Actinic Keratosis on 250 cm2 of Skin on Trunk and Extremities: A Randomized Dose-Finding Trial

Abstract

Background: Field treatment of actinic keratosis (AK) can eradicate clinical and sub-clinical lesions; treatments for extended skin areas are required.Methods: This randomized, double-blind, vehicle-controlled trial (NCT01998984) evaluated ingenol mebutate (IngMeb) 0.06% gel for AK treatment over extended areas. Adults with 5–20 AK lesions within a 250 cm2 area of skin on the trunk (except chest) or extremities were randomized to: 2 days vehicle, 2 days IngMeb (2D, n=55); 1 day vehicle, 3 days IngMeb (3D, n=59); 4 days IngMeb (4D, n=49); or 4 days vehicle (n=61). Week 8 primary endpoint was complete clearance of AK lesions; secondary endpoints included reduction in AK count and partial clearance. Adverse events (AEs) were recorded and local skin responses (LSRs) assessed. A hierarchical testing scheme, starting with 3D versus vehicle, was used.Results: In total, 224 patients were randomized. At Week 8, for 2D, 3D, 4D, and vehicle groups, complete clearance rates were 12.7%, 5.1%, 26.8%, and 0.0% (3D vs. vehicle, p=0.18); reductions in AK count were 63.0%, 66.8%, 73.6%, and 11.9%, respectively. LSR scores peaked at Day 5 (3D and 4D), and Days 5 and 10 (2D). Application-site pain and pruritus were common AEs. Of 15 neoplasm AEs, 14 were designated keratoacanthomas and one squamous cell carcinoma by central pathological review. The 4D group was closed based on pre-defined criteria.Conclusions: All three regimens were effective at reducing AK count on trunk/extremities. The 4D treatment was not well tolerated. Complete clearance was not significantly different to vehicle.