BACKGROUND: The tubulin polymerization and Src kinase signaling inhibitor 
tirbanibulin is being investigated as a topical treatment for actinic keratosis, 
a precursor of squamous-cell carcinoma.
METHODS: In two identically designed double-blind trials, we randomly assigned, 
in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive 
either topical tirbanibulin or vehicle (placebo) ointment. The ointment was 
applied by the patients to a 25-cm2 contiguous area containing four to eight 
lesions once daily for 5 consecutive days. The primary outcome was the 
percentage of patients with a complete (100%) reduction in the number of lesions 
in the application area at day 57. The secondary outcome was the percentage of 
patients with a partial (≥75%) reduction in the number of lesions within the 
application area at day 57. The incidence of recurrence was evaluated at 1 year. 
Local reactions were scored with the use of 4-point scale (ranging from 0 
[absent] to 3 [severe]).
RESULTS: A total of 702 patients were enrolled in the two trials (351 patients 
per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 
175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle 
group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; 
P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 
of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; 
P<0.001). The percentages of patients with partial clearance were significantly 
higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the 
estimated percentage of patients with recurrent lesions was 47% among patients 
who had had a complete response to tirbanibulin. The most common local reactions 
to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 
82%. Adverse events with tirbanibulin were application-site pain in 10% of the 
patients and pruritus in 9%, all of which resolved.
CONCLUSIONS: In two identically designed trials, tirbanibulin 1% ointment 
applied once daily for 5 days was superior to vehicle for the treatment of 
actinic keratosis at 2 months but was associated with transient local reactions 
and recurrence of lesions at 1 year. Trials comparing tirbanibulin with 
conventional treatments and that have longer follow-up are needed to determine 
the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; 
ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).