Adapalene Gel 0.1% Versus Placebo as Prophylaxis for Anti‐Epidermal Growth Factor Receptor‐Induced Acne‐Like Rash: A Randomized Left‐Right Comparative Evaluation (APPEARANCE)

LESSONS LEARNED. The results of the APPEARANCE trial indicate that adapalene does not prevent acne‐like rash over placebo when added to topical moisturizer and oral minocycline but instead may have a detrimental effect. Therefore, adapalene is not recommended as prophylaxis against acne‐like rash induced by anti‐epidermal growth factor receptor therapies. Given that acne‐like rash was completely controlled with placebo in approximately half of patients, predictive measures to identify patients needing intensive prophylaxis are required. BACKGROUND. Anti‐epidermal growth factor receptor (EGFR) therapies are frequently associated with acne‐like rash. To evaluate the prophylactic efficacy of adapalene, a topical retinoid used as first‐line therapy for acne vulgaris, we conducted a randomized, placebo‐controlled, evaluator‐blinded, left‐right comparative trial. METHODS. Patients with non‐small cell lung, colorectal, or head and neck cancer scheduled to receive anti‐EGFR therapies were randomly assigned to once‐daily adapalene application on one side of the face, with placebo on the other side. All patients had topical moisturizer coapplied to both sides of the face, and received oral minocycline. The primary endpoint was the difference in total facial lesion count of acne‐like rash at 4 weeks. Secondary endpoints included complete control rate (CCR) of acne‐like rash (≤5 facial lesions) and global skin assessment (Investigator's Global Assessment [IGA] scale, grade 0–4) at 4 weeks. Two blinded dermatologists independently evaluated the endpoints from photographs. RESULTS. A total of 36 patients were enrolled, of whom 26 were evaluable. Adapalene treatment was associated with a greater lesion count than placebo at 4 weeks, although the difference was not statistically significant (mean, 12.6 vs. 9.8, p = .12). All four patients with a difference >10 in lesion count between face sides had a greater count on the adapalene‐treated side. No significant differences were observed in CCR of acne‐like rash (54% vs. 50%) or IGA scale (mean grade, 1.9 vs. 1.7) between the adapalene and placebo sides. CONCLUSION. Adapalene is not recommended as prophylaxis against acne‐like rash induced by anti‐EGFR therapies.