e20049 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the frontline treatment of choice for patients with EGFR-mutant non-small cell lung cancer (NSCLC). However, EGFR-TKIs are associated with unique and dramatic dermatologic side effects that negatively impact patients’ quality of life, potentially resulting in poor adherence, including dose reductions or premature treatment cessation. Thus, it is crucial for the oncologists to be familiar with the array of dermatologic manifestations caused by these drugs for effective patient management. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for phase 3 randomized controlled trials (RCTs) comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with NSCLC. We calculated the odds ratio (OR) of all- and high-grade 10 dermatologic adverse events (dAEs). We conducted a meta-analysis using a random-effects model to compare the risk of dAEs in patients receiving EGFR-TKIs versus placebo/chemotherapy. Subgroup analysis based on control arm (placebo or chemotherapy) and individual EGFR-TKIs (afatinib, dacomitinib, erlotinib, gefitinib of osimertinib) were conducted. Results: 35 RCTs comprising 16,151 patients were included. In addition to all- and high-grade rash (all-grade: 12.21, 95% CI: 9.00-16.56; high-grade: OR 7.83, 95% CI: 5.11-12.00), EGFR-TKIs were associated with a significantly increased risk of all-grade acne (OR 12.24, 95% CI: 3.11-48.2), dermatitis acneiform (OR 8.46, 95% CI: 4.03-17.8), dry skin (OR 6.15, 95% CI: 4.02-9.40), palmar-plantar erythrodysesthesia syndrome (OR 11.14, 95% CI:3.00-41.4), paronychia (OR 31.97, 95% CI: 17.9-57.1), pruritus (OR 2.86, 95% CI: 2.17-3.77), skin exfoliation (OR 7.62, 95% CI: 2.55-22.8), and skin fissures (OR 11.59, 95% CI:4.86-27.6). The increased risk of EGFR-TKI-related dAEs was more prominent when compared with chemotherapy than placebo. In subgroup analyses of individual EGFR-TKIs, the risk of high-grade rash was significantly increased in patients treated with erlotinib or gefitinib but not in those treated with other EGFR-TKIs. Conclusions: This is the most comprehensive meta-analysis summarizing currently available evidence on cutaneous toxicity profile of EGFR-TKIs. These findings provide physicians with a better understanding for prompt recognition and management of these dAEs, to avoid unnecessary dose modifications and/or termination, and to prevent impairments in patients' quality of life.