DISCUSSION
toxicity, infections, rash, paronychia, keratinization, skin toxicities, cutaneous toxicity, skin toxicity
SKIN, INFECTIONS, PARONYCHIA, SKIN TOXICITIES, SKIN TOXICITY
This was a prospective interventional study with prophylactic treatment to reduce skin toxicity associated with dacomitinib treatment. A total of 41 patients participated, and skin toxicities of Grade ≥2 were observed in 18/41 patients (43.9%; 90% CI, 31.2%–56.7%) during the initial 8 weeks of treatment. The primary endpoint failed to achieve statistical significance because the upper limit of the 90% CI exceeded the pre‐planned threshold of 46%.The representative skin toxicities with Grade ≥2 in this study were acneiform rash (26.8%) and paronychia (12.2%), which were less than the rates of 33% and 42% in the overall population of the ARCHER1050 study.Cohort I in ARCHER1042, which was used as the basis for the statistical design of this study, consisted mostly of non‐Asians, accounting for 97.3% of the enrolled participants. The enzymatic activity of the main metabolizing enzyme of dacomitinib, CYP2D6, is known to differ across races. Asians have a high frequency (41%) of a reduced function allele, CYP2D6*10, which is rarely present in Caucasians.Cutaneous side effects induced by EGFR‐TKIs are due to the inhibition of EGFR in basal keratinocytes and hair follicles. Disturbance of terminal keratinocyte differentiation and keratinization of the follicular epithelium results in occlusion of the follicular orifice, causing an acne‐like skin rash.Individuals of Asian descent, owing to their comparably thinner stratum corneum,Adherence to both oral and topical prophylaxis medications was good, with perfect compliance in 80% of the patients throughout the 8 weeks. Adherence to treatment is crucial for improving quality of life and obtaining optimal outcomes.Skin problems are a challenge in continuing treatment with EGFR inhibitors; 90% of patients develop skin problems, 76% require treatment interruption, 60% require dose reduction, and 32% require treatment discontinuation.Response rates were similar to those of other trials in both patients previously treated with EGFR‐TKI and EGFR‐TKI‐naïve patients.The most established prophylaxis for cutaneous toxicity is oral tetracyclines, which prevent and overcome infections.This study has some limitations. First, the study had an open‐label, single‐arm design, which could have introduced bias. We tried to educate the patients uniformly using an instruction guide, and we evaluated medication adherence based on patient diaries. Second, previously treated patients were enrolled. Ideally, medication adherence and skin toxicity evaluation should be limited to EGFR‐TKI‐naive patients. In the analyses of the association between skin toxicities and patients' characteristics, no significant correlation was observed. Third, since adherence was good at 8 weeks in this study, concurrently prophylaxis must continue during ongoing EGFR‐TKI therapy. Further study is awaited about long‐term adherence and toxicity management.This study prospectively evaluated the efficacy of comprehensive prophylaxis for dacomitinib‐related skin toxicity in the Japanese population. Although no significant differences were observed, the study may have been effective considering the racial differences in skin toxicity. The prevention of skin toxicity and patient education are important for the maintenance of quality of life and continuity of treatment.