Comparative Analysis of Prevention versus Non-Prevention for Skin Toxicities on Clinical Outcomes in Non- Small Cell Lung Cancer (NSCLC) Patients Treated with Erlotinib: A 10-year Retrospective Cohort Study

Introduction: Erlotinib is an established first-line therapy for Epidermal Growth Factor Receptor ( EGFR ) mutant non-small cell lung cancer (NSCLC). However, dermatologic toxicities are common and lead to treatment interruption and reduced adherence. Evidence regarding the impact of prophylactic skin toxicity management on clinical effectiveness remains limited. Aim To compare the incidence and severity of skin toxicities, treatment modifications, and clinical outcomes between NSCLC patients receiving prophylactic skin toxicity and those without prophylactic during erlotinib therapy. Methods A retrospective cohort study was conducted among EGFR -mutant NSCLC patients treated with erlotinib at Surat Thani Hospital from 2015 to 2025. Patients were categorized into prevention and non-prevention groups based on receipt of prophylactic interventions. Associations with toxicity severity, objective response rate (ORR), and treatment discontinuation were evaluated using Chi-square tests, and multivariate logistic regression was performed to adjust for confounders. Propensity score matching (PSM) was applied for progression-free survival (PFS) and time to first skin toxicity. Kaplan–Meier estimates and log-rank tests were used for time-to-event analyses. Results A total of 265 patients were included. Severe toxicity was significantly lower in the prevention group (6.1% vs 25.0%, p = 0.011). Temporary and permanent erlotinib discontinuation were significantly lower in the prevention group (3.1% vs 42.9% and 48.2% vs 67.1%, p < 0.001 and p = 0.009, respectively). ORR was higher in the prevention group (63.1% vs 40.0%, p = 0.002). After PSM, PFS remained significantly longer in the prevention group (p = 0.00032), whereas time to first skin toxicity did not differ. Conclusion Prophylactic skin toxicity management reduces severe dermatologic events, decreases treatment interruption, improves ORR, and prolongs PFS without affecting rash onset. These findings support integrating structured prophylactic skin toxicity into routine erlotinib treatment.