The efficacy and safety of aminolevulinic acid 20% topical solution activated by pulsed dye laser and blue light for the treatment of facial cutaneous squamous cell carcinoma in situ Mark S Nestor1–3; Haowei Han1; Faraz Yousefian1; Ciaran Smythe1 1Center for Clinical and Cosmetic Research, Aventura, FL; 2Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; 3Department of Surgery, Division of Plastic Surgery, University of Miami Miller School of Medicine, Miami, FL INTRODUCTION • Squamous cell carcinoma (SCC) is the second most common cutaneous malignancy1 • Aminolevulinic acid (ALA) 20% solution–photodynamic therapy (ALA-PDT) is approved for the treatment of actinic keratoses on the face, scalp, and upper extremities2 and is a potential treatment option for SCC OBJECTIVE • This study evaluated the efficacy, tolerability, and safety of ALA-PDT in combination with pulsed dye laser (PDL) for the treatment of facial cutaneous SCC in situ (isSCC) METHODS Study design and participants • A prospective, single-center, investigator-initiated, open-label pilot clinical trial (NCT02137785) was conducted at the Center for Clinical and Cosmetic Research in 2020–2021 • Patients with biopsy-confirmed isSCC on the face were included in the study • Only lesions with a diameter of 0.4–1.3 cm were considered for the study • Patients with infiltrative, severe, metaplastic, or recurrent isSCC were excluded from the study Figure 1. Imaging of isSCC in 2 patients obtained (A) before and (B) after treatment with ALA-PDL-PDT A) Visit 1 (Pretreatment) Patient A Patient B B) Visit 10 (Posttreatment) Patient A Patient B A) Visit 1 (Pretreatment) Patient A Patient B B) Visit 10 (Posttreatment) Patient A Patient B ALA, aminolevulinic acid; PDL, pulsed dye laser; PDT, photodynamic therapy; isSCC, squamous cell carcinoma in situ. Tolerability • Median LSR scores peaked within 1 week following each treatment session and steadily decreased afterward (Table 1) — The most common LSRs were erythema and scaling • The mean ± standard deviation posttreatment pain score was 2.95 ± 2.97 Table 1. Median local skin reaction scores for the lesion areas Visit number 1 (Pre-Tx #1) 3 (Tx #1) 4 5 6 (Pre-Tx #2) 7 (Tx #2) 8 9 10 EOT Erythema 2 3 3 2 2 3 3 2 1 Flaking/scaling 1 1 1 1 1 0.5 1 0.5 0 Crusting 0 0 0 0 0 0 0 0.5 0 Swelling 0 0 0 0 0 0 0 0 0 Vesiculation/ pustulation 0 0 0 0 0 0 0 0 0 Erosion/ ulceration 0 0 0 0 0 0 0 0 0 Data shown as median LSRs for the lesion areas. Responses were scored on a scale from 0 (not present) to 4 (high severity). EOT, end of treatment; LSR, local skin reaction; Tx, treatment. Safety • The majority of treated patients (65%) did not experience any AEs • Reported AEs included allergic contact dermatitis, blurry vision, right ear pain, right leg cellulitis, double vision, hypotension, and wound site infection — None of the reported AEs were serious or considered related to study treatment • No patients withdrew from the study CONCLUSIONS • The primary and secondary efficacy endpoints of histological and clinical clearance were achieved in a majority of patients by the end of ALA-PDL-PDT treatment • ALA-PDL-PDT was well tolerated and safe REFERENCES 1) Voiculescu V, et al. Dis Markers. 2016;2016:4517492. 2) LEVULAN® KERASTICK® (aminolevulinic acid HCl) for topical solution, 20%. Full prescribing information. Sun Pharmaceutical Industries, Inc. 2020. ACKNOWLEDGMENTS This investigator-initiated trial was funded by Sun Pharma. Medical writing support was provided by AlphaBioCom, LLC, and funded by Sun Pharma. DISCLOSURES MN received a research grant from Sun Pharma. HH, FY, and CS report nothing to disclose. Treatments and procedures • ALA 20% topical solution was applied to the lesion and adjacent skin and incubated for 18–24 hours, followed by PDL treatment (pulse duration: 0.45 milliseconds, fluence: 13 J/cm2, amount determined by the investigator) and then blue light illumination (BLU-U®; 10 J/cm2 for 16 minutes 40 seconds) • Patients underwent 2 ALA-PDL-PDT treatment sessions separated by a 30-day period • The lesion was surgically excised for histological assessment 4–6 weeks following the second treatment Assessments and endpoints • The primary efficacy endpoint was the proportion of patients achieving histological clearance of isSCC at the end of treatment/surgical excision • Tolerability was assessed from local skin reactions (LSRs) and patient-reported lesion site pain — Lesion site pain was measured using a visual analog scale ranging from 0 (no pain) to 10 (worst pain possible) within 15 minutes of each treatment session • Safety was assessed from frequency of adverse events (AEs) RESULTS Efficacy • Of 20 enrolled patients, 17 (85%) achieved histological clearance at the end of treatment • After excluding two patients with residual isSCC exhibiting skip lesions, the histological clearance rate was 17/18 patients (94%) • Images obtained during visit 1 (pretreatment; Figure 1A) and visit 10 (posttreatment; Figure 1B) show clinical clearance of isSCC with ALA-PDL-PDT