Radiotherapy versus imiquimod for complex lentigo maligna: A phase 3 randomized clinical trial

Angela M Hong; Serigne N Lo; Gerald B Fogarty; Jonathan Stretch; Wei Wang; Pablo Fernandez-Penas; Richard C W Martin; Matthew Foote; H Peter Soyer; Jeremy Ruben; Victoria Mar; Lilian Rocha; Cyro Festa-Neto; Chris Wratten; Sam Hogarth; Helena Collgros; Amanda Glanz; Bruna Melhoranse Gouveia; Richard A Scolyer; Madeleine T King; Pascale Guitera

doi:10.1016/j.jaad.2025.07.028

Radiotherapy versus imiquimod for complex lentigo maligna: A phase 3 randomized clinical trial

J Am Acad Dermatol. 2025 Nov;93(5):1251-1260. doi: 10.1016/j.jaad.2025.07.028. Epub 2025 Jul 17.

Authors

Angela M Hong¹, Serigne N Lo², Gerald B Fogarty³, Jonathan Stretch², Wei Wang⁴, Pablo Fernandez-Penas⁵, Richard C W Martin⁶, Matthew Foote⁷, H Peter Soyer⁸, Jeremy Ruben⁹, Victoria Mar¹⁰, Lilian Rocha¹¹, Cyro Festa-Neto¹¹, Chris Wratten¹², Sam Hogarth¹³, Helena Collgros¹⁴, Amanda Glanz¹⁵, Bruna Melhoranse Gouveia², Richard A Scolyer¹⁶, Madeleine T King¹⁷, Pascale Guitera¹⁸

Affiliations

¹ Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. Electronic address: angela.hong@sydney.edu.au.
² Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
³ Icon Cancer Centre Revesby, Revesby, New South Wales, Australia.
⁴ Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Department of Radiation Oncology, Westmead Hospital, Westmead, New South Wales, Australia.
⁵ Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Department of Dermatology, Westmead Hospital, Westmead, New South Wales, Australia.
⁶ Te Whatu Ora-Waitemata, Department of Cutaneous Oncology, University of Auckland, Auckland, New Zealand.
⁷ Department of Radiation Oncology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
⁸ Frazer Institute, The University of Queensland, Dermatology Research Centre, Brisbane, Queensland, Australia; Department of Dermatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
⁹ Department of Radiation Oncology, Alfred Health, Melbourne, Victoria, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
¹⁰ School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Victorian Melanoma Service, Alfred Health, Melbourne, Victoria, Australia.
¹¹ Department of Dermatology, Hospital das Clínicas of São Paulo University, São Paulo, Brazil.
¹² School of Medicine and Public Health, College of Health Medicine and Wellbeing, University of Newcastle, Callaghan, New South Wales, Australia; Radiation Oncology Department, Calvary Mater Newcastle, Waratah, New South Wales, Australia.
¹³ Melanoma and Skin Cancer Trials Ltd, Melbourne, Victoria, Australia.
¹⁴ Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, New South Wales, Australia.
¹⁵ Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, New South Wales, Australia.
¹⁶ Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
¹⁷ School of Psychology, The University of Sydney, Sydney, New South Wales, Australia.
¹⁸ Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, New South Wales, Australia.

PMID: 40683357
DOI: 10.1016/j.jaad.2025.07.028

Abstract

Background: For patients with lentigo maligna who are not suitable for surgery, radiotherapy, or topical imiquimod are alternative nonsurgical treatments.

Objective: This trial aimed to assess the efficacy, safety, and patient-reported health-related quality of life (HRQL).

Methods: A multiinstitutional, phase 3, randomized trial conducted between August 2015 and November 2021. Patients were randomized to radiotherapy or imiquimod. The primary end point was treatment failure at 24 months. Secondary end points included response at 6 months, development of invasive disease, toxicity and HRQL.

Results: Between August 2015 and November 2021, 126 patients were randomized. The response rate was 95% at 6 months in both groups. The treatment failure rates were low with 12 failures in the radiotherapy group and 6 in the imiquimod group at 24 months (Odd ratios, 2.35; 95% CI, 0.82-6.75; P = .11). Both were well-tolerated with mainly grade 1 and 2 acute skin toxicity with no significant differences between groups in skin symptoms or HRQL at long-term. Patients had significantly better emotional scores after treatment than at baseline in both groups. The trial is underpowered due to early cessation of recruitment.

Conclusions: Both radiotherapy and imiquimod are efficient and well-tolerated treatments for lentigo maligna. Neither have negative impacts on HRQL at 24 months.

Keywords: imiquimod; lentigo maligna; melanoma in situ; radiotherapy.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Multicenter Study
Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Antineoplastic Agents* / adverse effects
Antineoplastic Agents* / therapeutic use
Female
Humans
Hutchinson's Melanotic Freckle* / drug therapy
Hutchinson's Melanotic Freckle* / pathology
Hutchinson's Melanotic Freckle* / radiotherapy
Hutchinson's Melanotic Freckle* / therapy
Imiquimod* / administration & dosage
Imiquimod* / adverse effects
Imiquimod* / therapeutic use
Male
Middle Aged
Patient Reported Outcome Measures
Quality of Life
Skin Neoplasms* / drug therapy
Skin Neoplasms* / pathology
Skin Neoplasms* / radiotherapy
Skin Neoplasms* / therapy
Treatment Failure
Treatment Outcome

Substances

Imiquimod
Antineoplastic Agents