First‐line epidermal growth factor receptor (<scp>EGFR</scp>)–tyrosine kinase inhibitor alone or with whole‐brain radiotherapy for brain metastases in patients with <scp>EGFR</scp>‐mutated lung adenocarcinoma

<jats:p>We proposed to compare the outcomes of first‐line epidermal growth factor receptor–tyrosine kinase inhibitor (<jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content>) alone with <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> plus whole‐brain radiotherapy (<jats:styled-content style="fixed-case">WBRT</jats:styled-content>) for the treatment of brain metastases (<jats:styled-content style="fixed-case">BM</jats:styled-content>) in patients with <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐mutated lung adenocarcinoma. A total of 1665 patients were screened from 2008 to 2014, and 132 were enrolled in our study. Among the 132 patients, 72 (54.5%) harbored a deletion in exon 19, 97 (73.5%) showed multiple intracranial lesions, and 67 (50.8%) had asymptomatic <jats:styled-content style="fixed-case">BM</jats:styled-content>. Seventy‐nine patients (59.8%) were treated with <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> alone, 53 with concomitant <jats:styled-content style="fixed-case">WBRT</jats:styled-content>. The intracranial objective response rate was significantly higher in the <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> plus <jats:styled-content style="fixed-case">WBRT</jats:styled-content> treatment group (67.9%) compared with the <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> alone group (39.2%) (<jats:italic>P</jats:italic> = 0.001). After a median follow‐up of 36.2 months, 62.1% of patients were still alive. The median intracranial <jats:styled-content style="fixed-case">TTP</jats:styled-content> was 24.7 months (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 19.5–29.9) in patients who received <jats:styled-content style="fixed-case">WBRT</jats:styled-content>, which was significantly longer than in those who received <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> alone, with the median intracranial <jats:styled-content style="fixed-case">TTP</jats:styled-content> of 18.2 months (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>, 12.5–23.9) (<jats:italic>P</jats:italic> = 0.004). There was no significant difference in overall survival between <jats:styled-content style="fixed-case">WBRT</jats:styled-content> and <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> alone groups, (median, 48.0 <jats:italic>vs</jats:italic> 41.1 months; <jats:italic>P</jats:italic> = 0.740). The overall survival is significantly prolonged in patients who had an intracranial <jats:styled-content style="fixed-case">TTP</jats:styled-content> exceeding 22 months compared to those who developed intracranial progression <22 months after treatment, (median, 58.0 <jats:italic>vs</jats:italic> 28.0 months; <jats:italic>P</jats:italic> = 0.001). For <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐mutated lung adenocarcinoma patients with <jats:styled-content style="fixed-case">BM</jats:styled-content>, treatment with concomitant <jats:styled-content style="fixed-case">WBRT</jats:styled-content> achieved a higher response rate of <jats:styled-content style="fixed-case">BM</jats:styled-content> and significant improvement in intracranial progression‐free survival compared with <jats:styled-content style="fixed-case">EGFR</jats:styled-content>‐<jats:styled-content style="fixed-case">TKI</jats:styled-content> alone.</jats:p>