Efficacy of imiquimod in the management of lentigo maligna.

Abstract

10074 Background: Lentigo maligna (LM), a melanocytic proliferation occurring on photoexposed skin, might progress to LM melanoma. Surgery is recommended as first-line treatment. However, the main challenge is the size of the excision inducing often-aesthetic injuries on the face and thus often refused by patients. The excision margins of 5 to 10 mm remain without international consensus. Several studies have shown that imiquimod induced LM regression, acting by enhancing IFN-γ production and effector function of T cells. The main goal of this study is to investigate the effect of imiquimod versus placebo in neoadjuvant setting to decrease the excision size as from the first surgical procedure. Methods: We performed a prospective, randomized, open, multicenter, phase III clinical study (NCT01720407). The health authority and ethics committee approvals were obtained and all subjects signed an informed consent. The primary endpoint was to demonstrate that in neoadjuvant situation, imiquimod could reduce the surgical excision size of LM with a healthy tissue margin of 5 mm. The main inclusion criteria were: Patients > 18 years fit for surgery. LM of the head histologically confirmed and not previously treated. Surface lesion ≥ to 1cm² and ≤ to 20cm². The two treatment arms were imiquimod or placebo followed by LM excision. Imiquimod or placebo were applied once daily, 5 days/week for 4 weeks followed by 5 mm margin surgery performed four weeks after the last treatment application. For sample size, 268 patients were expected to demonstrate a difference of 15% between the two arms in a bilateral situation with an alpha risk of 5% and a beta risk of 20%. Results: The trial involved 273 patients, 238 (105 men (44%) and 133 women (56%), mean age of 71 ± 10.2 years, were analyzed in modified ITT. Statistical analysis was performed on 122 patients in the imiquimod arm and 116 patients in the placebo arm. For the primary endpoint, the first extralesionnal excision has been achieved for 112 (91.8%) patients in the imiquimod arm and for 98 (84.5%) placebo patients group. There was no significant difference (p value = 0.1067) between the two arms. However, regarding the surface of LM, imiquimod allowed a highly significant reduction (4.2 cm² ± 4.6 to 2.3 cm² ± 3.3) compared to LM treated by placebo (4.0 cm² ± 3.5 to 4.0 cm² ±3.3; p < 0.0001). Conclusions: This randomized prospective study shows that imiquimod reduces the LM area (-50%) after one month of treatment. Reducing the surface of LM with imiquimod is not associated with a higher risk of intralesional excision (marge 5mm), with a significant esthetic result (less excised surface). Clinical trial information: NCT01720407.