Impact of prophylactic skin toxicity management on treatment continuity and clinical outcomes in EGFR-mutant non-small cell lung cancer treated with osimertinib: a 7-year real-world retrospective cohort study

Osimertinib is the preferred epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for patients with EGFR-mutant non-small cell lung cancer (NSCLC) due to its superior efficacy and favorable safety profile. Nevertheless, dermatologic toxicities remain common and may disrupt treatment continuity, underscoring the importance of effective supportive care. Evidence regarding the clinical impact of proactive skin toxicity management during osimertinib therapy in real-world settings remains limited.

To evaluate the association between proactive versus reactive skin toxicity management and toxicity severity, treatment modification, and clinical outcomes in patients with EGFR-mutant NSCLC treated with osimertinib.

This retrospective cohort study included adult patients with advanced or recurrent EGFR-mutant NSCLC who received osimertinib at Surat Thani Hospital between January 2019 and January 2026. Patients were classified into a proactive skin toxicity management group, in which supportive skin care was initiated at the start of osimertinib therapy, or a reactive management group, in which skin toxicity management was initiated after the onset of dermatologic adverse events. Skin toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Multivariate logistic regression was used to evaluate the associations between skin toxicity management strategy (proactive vs reactive) and skin toxicity severity, osimertinib treatment modification, and objective response rate. Progression-free survival (PFS) was analyzed using Kaplan–Meier methods and Cox proportional hazards models.

A total of 120 patients were included (60 per group), with comparable baseline characteristics. The overall incidence of skin toxicity did not differ between the proactive and reactive management groups (60.0% vs 53.3%, p = 0.290). However, proactive management was independently associated with a substantially lower risk of severe skin toxicity (adjusted odds ratio [OR] 0.122; 95% confidence interval [CI] 0.022–0.681; p = 0.006). Temporary and permanent treatment discontinuations due to skin toxicity were significantly reduced in the proactive group (both p < 0.001). Patients receiving proactive management demonstrated a higher objective response rate (78.3% vs 38.3%; adjusted OR 5.640; p < 0.001) and longer median PFS (14.0 vs 10.0 months; hazard ratio 0.313; 95% CI 0.163–0.600; p < 0.001).

Proactive skin toxicity management during osimertinib therapy does not reduce the incidence of dermatologic adverse events but significantly mitigates toxicity severity, improves treatment continuity, and is associated with superior clinical outcomes compared with reactive management. These findings highlight the clinical value of proactive, supportive care-oriented skin management strategies to optimize osimertinib treatment in routine oncology practice.