Prophylactic treatment of dacomitinib‐induced skin toxicities in epidermal growth factor receptor‐mutated non–small‐cell lung cancer: A multicenter, Phase II trial

BACKGROUND: Dacomitinib significantly improves progression‐free survival and overall survival (OS) compared with gefitinib in patients with non–small‐cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)‐activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. METHODS: We performed a single‐arm, prospective, open‐label, multi‐institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR‐activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. RESULTS: In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32–83 years), 20 were male, and 36 had a performance status of 0–1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%–56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression‐free survival was 6.8 months (95% CI, 4.0–8.6 months) and median OS was 21.6 months (95% CI, 17.0 months–not reached). CONCLUSION: Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.