Photodynamic therapy for actinic keratosis of the forehead and scalp: a randomized, controlled, phase II clinical study evaluating the non-inferiority of a new protocol involving irradiation with a light-emitting, fabric-based device (the Flexitheralight protocol) compared with the conventional protocol involving irradiation with the Aktilite CL 128 lamp. C. Vicentini1, 2, AS. Vignion-Dewalle1, E. Thecua1, F. Lecomte1, C. Maire1, 2, P. Deleporte1, H. Béhal3, D. Kerob4, A. Duhamel3, S. Mordon1, L. Mortier1, 2 1Univ. Lille, INSERM, CHU Lille, U1189 – ONCO-THAI, Lille, France 2Department of Dermatology, CHU Lille, Lille, France 3Univ. Lille, CHU Lille, EA 2694, Lille, France 4Galderma International SAS, La Défense, France British Journal of Dermatology. DOI: 10.111/bjd.17350

AS. Vignion-Dewalle, Research engineer

Introduction What’s already known? Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is an effective and non-invasive treatment for actinic keratosis (AK). Treatment-associated pain is frequently experienced by patients treated with the conventional protocol (C-PDT). PDT using daylight (D-PDT) as the activating light source has been confirmed as equally effective and less painful than C-PDT, but it cannot be performed in all weather conditions.

Objective Primary objective: To assess the non-inferiority, in terms of efficacy at three months, of a new PDT protocol applying irradiation with a light-emitting, fabric-based device (FLEXI-PDT) compared to C-PDT for treating AK. Key secondary objective: To compare pain scores between FLEXI-PDT and C-PDT. Other secondary objectives: To evaluate the adverse effects at seven days To evaluate the lesion complete response rate at six months To evaluate the cosmetic outcome at three and six months To evaluate the patient satisfaction

Methods Study design: Monocentric, randomized, controlled, non-inferiority clinical study. Study population: Patients with two treatment areas with a similar number and grade of AK lesions (from 5 to 7 lesions), randomized to receive either FLEXI-PDT or C-PDT. Treatment regimen:

Methods Treatment course:

Methods Evaluation course / endpoints: Day 1: Primary objective If the lower limit of the 95% confidence interval (CI) of the absolute difference in lesion complete response rates at three months between FLEXI-PDT and C-PDT was less than the absolute margin of non-inferiority stated to -10%, FLEXI-PDT was declared non-inferior to C-PDT Evaluation course / endpoints: Day 1: Pain scores at the end of irradiation (from 0: no pain to 10: worst pain) Day 7: Adverse effects Month 3: Lesion complete response (complete vs. incomplete response) Cosmetic outcome (“excellent”, “good”, “fair”, or “poor”) Month 6:

Results Efficacy: The lower limit of the 95% CI was higher than -10% → The non-inferiority at three months of FLEXI-PDT compared to C-PDT was supported (primary objective) The same finding was obtained at six months

Results Pain: Pain scores significantly lower for FLEXI-PDT compared to C-PDT → The superiority in tolerability of FLEXI-PDT compared to C-PDT was supported (key secondary objective) Pain scores close to zero for FLEXI-PDT → FLEXI-PDT is nearly pain-free

Results Others secondary objectives: Similar local side effects for FLEXI-PDT and C-PDT Similar cosmetic outcomes between FLEXI-PDT and C-PDT Higher patient satisfaction and preference for FLEXI-PDT compared to C-PDT

Discussion This study found: The significant non-inferiority in efficacy of FLEXI-PDT compared to C-PDT The significant better tolerability of FLEXI-PDT compared to C-PDT A lower lesion complete response rate at three months for C-PDT (59.1%) lower than most rates reported in the literature due to a larger proportion of ─ less responsive to PDT ─ grade II AK in the present study

Discussion Limits of the study: The unblinding of the study The early termination of the study due to the initiation of the PHOS-ISTOS clinical study aiming to assess an improved version of FLEXI-PDT → Reduction in the a priori statistical power of the study for the primary endpoint http://www.phosistos.com/

Conclusions What does this study add? This study demonstrates that the Flexitheralight protocol, which can be performed in all weather conditions, is equally effective as the conventional photodynamic therapy protocol for actinic keratosis and is a less painful technique.

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