Effect of topical imiquimod as primary treatment for lentigo maligna - the LIMIT-1 study

SummaryBackground Topical imiquimod is sometimes used for lentigo maligna (LM) in-situ melanoma instead of surgery, but frequency of cure is uncertain. Pathological complete regression (pCR) is a logical surrogate marker for cure after imiquimod, although residual LM and atypical melanocytic hyperplasia may not be reliably distinguished. A trial comparing imiquimod versus surgery might be justified by a high imiquimod pCR rate. Objectives Primary: to estimate pCR rate for LM following imiquimod. Secondary: to assess accuracy of prediction of pCR, using clinical complete regression (cCR) plus negative post-treatment biopsies, tolerability, resource use, patients’ preferences; and induced melanoma immunity. Methods This was a single arm phase II trial of 60 imiquimod applications over12 weeks for LM then radical resection. A pCR rate ≥25/33 would reliably discriminate between pCR rates <60% and ≥85%. Clinical response was assessed and biopsies taken after imiquimod. Patients recorded adverse events in diaries. Patient preference was measured after surgery using a standard gamble tool. Results The pCR rate was 10/27 (37%, 95% CI 19%, 58%). The rate of cCR plus negative biopsies was 12/28 of whom 7/11 had pCR on subsequent surgery. Median dose intensity was 86.7%. Of surveyed patients, 8/16 preferred primary imiquimod over surgery if the cure rate for imiquimod was 80% and 4/16 if it was ≤50%. Conclusions The pCR rate was insufficient to justify phase III investigation of imiquimod versus surgery. Clinical complete response and negative targeted biopsies left uncertainty regarding pathological clearance. Some patients would trade less aggressive treatment of LM against efficacy. This article is protected by copyright. All rights reserved.