Radiotherapy and imiquimod are efficient and well-tolerated non-surgical treatment options for patients with lentigo maligna (LM), according to the results of a study published in the Journal of the American Academy of Dermatology.

The multicenter, phase 3, randomized clinical trial (ClinicalTrials.gov Identifier: NCT02394132) evaluated the efficacy, toxicity, and health-related quality of life (HRQOL) of these 2 non-surgical treatments in adults with biopsy-proven LM who were not ideal for surgery.

The patients were randomly assigned in a 1:1 ratio to receive radiotherapy or imiquimod stratified by treatment center, extent of LM, and immunocompetence. They were followed up at 3 months post-index and then at 6, 12, 18, and 24 months from the end of treatment. The proportion of patients who had treatment failure up to 24 months from the end of treatment was the primary endpoint, which was defined as pathological confirmation of LM within or at the margin of the original field.

A total of 126 patients were included from 8 centers in Australia, New Zealand, and Brazil from August 2015 to November 2021. The final per-protocol analysis included 118 patients, of whom 58 received radiotherapy and 60 received imiquimod. Mean ages were 72.8 years in the radiotherapy group (41% men) and 70.2 years in the imiquimod group (46.7% men). The mean treatment duration was 4.4 weeks for radiotherapy and 11.8 weeks for imiquimod.

At 6 months, the response rates after biopsy were 95% for both treatment groups. The radiotherapy group had more patients with reflectance confocal microscopy at 24 months compared with the imiquimod group (90% vs 75%; P =.07). No significant difference was observed in treatment failure up to 24 months. At 24 months, 18 treatment failures occurred, including 12 patients (20.7%) in the radiotherapy group and 6 (10%) in the imiquimod group (odds ratio, 2.35; 95% CI, 0.82-6.75; P =.106).

At 4 weeks after radiotherapy, 10 patients had grade 2 or 3 dermatitis, 4 patients had grade 2 ulceration, and 2 patients had grade 2 alopecia. For the imiquimod group at 4 weeks post-treatment, 23 patients had moderate or severe erythema, 4 patients had moderate or severe ulceration, and 7 patients had moderate or severe pruritus.

Skin symptoms scores measuring the HRQOL were increased in the radiotherapy group compared with the imiquimod group at 3 months post-index. The mean difference of 9.2 points was 2.6 times greater than the minimally important difference of 3.5 but was not statistically significant (P =.063). The difference was reduced at 9 months post-index, as it was 6.7 before adjustment for multiple comparisons (P =.020).

Both groups had a similar trajectory of emotional bother, and improvement in emotional bother was clinically and statistically significant in the post hoc analysis (P <.001).

Limitations of the study include the nonblinded treatment allocation and relatively short follow-up. In addition, the trial was underpowered for the primary endpoint owing to early discontinuation during the COVID-19 pandemic.

“This is the first randomized trial comparing different treatment modalities in LM and the first HRQOL data to be published for LM. The response rates of both radiotherapy and imiquimod were very high at 95% based on the mandatory biopsy performed at 6 months after treatment and there were few recurrences in either group up to 24 months,” study authors concluded.