Twice weekly pulse and daily continuous‐dose erlotinib as initial treatment for patients with epidermal growth factor receptor–mutant lung cancers and brain metastases

<jats:sec><jats:title>BACKGROUND</jats:title><jats:p>In a phase 1 study of pulse/continuous‐dose erlotinib, no patient had disease progression in the central nervous system (CNS). This expansion cohort of the phase 1 study tested the same regimen in a cohort of individuals with epidermal growth factor receptor (<jats:italic>EGFR</jats:italic>)–mutant lung cancers with untreated brain metastases.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>Patients had not received EGFR tyrosine kinase inhibitors or radiation for brain metastases. All received 1200 mg of erlotinib on days 1 and 2 and 50 mg on days 3 to 7 weekly. The primary endpoints were the overall and CNS response rates (according to version 1.1 of the Response Evaluation Criteria in Solid Tumors).</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Between May 2015 and August 2016, 19 patients were enrolled. Forty‐two percent of the patients had target brain lesions, and the median size of the target brain lesions was 13 mm. Overall, 14 patients (74%; 95% confidence interval [CI], 51%‐89%) had partial responses. The response rate in brain metastases was 75%. The overall median progression‐free survival was 10 months (95% CI, 7 months to not reached). Only 3 patients (16%) had CNS progression. To date, 4 patients required CNS radiation at some time during their course. The adverse events (any grade) seen in 10% or more of the patients were rash, diarrhea, nausea, an increase in alanine aminotransferase, and fatigue.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>Pulse/continuous‐dose erlotinib produced a 74% overall response rate and a 75% response rate in brain metastases in patients with <jats:italic>EGFR</jats:italic>‐mutant lung cancers and untreated brain metastases. CNS control persisted even after progression elsewhere. Although this regimen did not improve progression‐free survival or delay the emergence of EGFR T790M, it prevented progression in the brain and could be useful in situations in which CNS control is critical. <jats:bold><jats:italic>Cancer</jats:italic> 2018;124:105‐9</jats:bold>. © <jats:italic>2017 American Cancer Society</jats:italic>.</jats:p></jats:sec>