A randomised, controlled, multicentre trial of imiquimod versus radiotherapy for lentigo maligna.

9502 Background: Lentigo maligna (LM) is a form of melanoma in situ that occurs mainly on sun exposed skin. For patients with LM who are not suitable for surgery due to location, size, patient preference or co-morbidities, topical imiquimod or radiotherapy are alternative non-surgical treatments. There are no prospective randomized controlled trial data to form the basis of any recommendations for the management of LM. This multi-institutional, international randomized phase 3 trial evaluated the efficacy and safety of imiquimod verus radiotherapy for patients with LM. The primary hypothesis was that treatment of LM with topical imiquimod would result in fewer treatment failures than radiotherapy. Methods: Patients aged > 18 years old with LM not suitable for surgery were randomly assigned (1:1) to imiquimod or radiotherapy. The primary endpoint was treatment failure within 24 months. Secondary endpoints included development of invasive disease within the area, side effects and patient-reported quality of life (QOL) assessed with validated questionnaires (skin-specific Skindex-16 and generic EQ-5D-5L). Results: Between August 2015 and November 2021, 126 patients were randomised from 8 centres (imiquimod 60, radiotherapy 58 in final analysis). The median age was 72 years and 94.9% of lesions were on the head and neck area. Median follow-up was 27 months (range 3-62 months). Six (10.5%) patients in the imiquimod group and 12 (24.0%) patients in the radiotherapy group developed recurrence within 24 months (OR 2.68, 95% CI, 0·92-7.8, p = 0.063). Median time to recurrence was not reached in either group. Treatment failure was significantly different within the subgroup of patients who had reflectance confocal microscopy (RCM) follow up of the LM (imiquimod 4/46, 8.7% radiotherapy 13/52 25.0%; OR 3.50 95% CI 1.05-11.65, p = 0.033). Only one RCM feature was associated with failure at 24 months and significantly different between treatment groups : the presence of atypical round cells at the dermal-epidermal junction (6.9 % of imiquimod failure and 27% of radiotherapy failure: p = 0.035). There were no differences between trial groups in patient-reported skin symptoms (itching, burning/stinging, pain, irritation), skin-specific emotional and functional QOL impacts, or generic QOL at any time points. Conclusions: Both imiquimod and radiotherapy are valid, well-tolerated and efficient non-surgical options for LM. There is no significant difference in the acute or long term QoL for the two treatments. Clinical trial information: NCT02394132 .